Implants using ultrasonic communication for neural sensing and stimulation

ABSTRACT

Described herein is an implantable medical device that includes a body having one or more ultrasonic transducers configured to receive ultrasonic waves and convert energy from the ultrasonic waves into an electrical energy, two or more electrodes in electrical communication with the ultrasonic transducer, and a clip attached to the body that is configured to at least partially surround a nerve and/or a filamentous tissue and position the two or more electrodes in electrical communication with the nerve. In certain examples, the implantable medical device includes two ultrasonic transducers with orthogonal polarization axes. Also described herein are methods for treating incontinence in a subject by converting energy from ultrasonic waves into an electrical energy that powers a full implanted medical device, and electrically stimulating a tibial nerve, a pudendal nerve, or a sacral nerve, or a branch thereof, using the fully implanted medical device.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.16/389,876, filed on Apr. 19, 2019, which claims priority benefit toU.S. Provisional Application No. 62/660,112, filed on Apr. 19, 2018,which is incorporated herein by reference for all purposes.

TECHNICAL FIELD

The present invention relates to implantable medical devices that arepowered by ultrasonic waves, and methods of using the implantablemedical device.

BACKGROUND

The peripheral nervous system of an individual operates activity ofvital organs and physiological homeostasis with tight control.Electrical pulses transmitted through nerves can alter, for example,pulse rates, inflammation, and bladder or bowel control. Certain medicalconditions can arise when these neural signals fail to properly controlthe body, either by over-stimulating or under-stimulating target organs.

Invasive methods have been developed for treating abnormal physiologicalactivity by controlling the electrical signals of the peripheral nervoussystem. Such methods can include implanting electrodes into the body ofa patient, with the tips of the electrodes contacting target nerves.These electrodes generally have long leads that attach to an externaldevice, which subject the patient to substantial risk of infection ordisplacement of the electrodes. Additionally, because many of themethods are so invasive, certain treatments are limited to clinicalsettings, and cannot be used as an at-home remedy. Wholly implantabledevices have been developed for less invasive treatment, but suchdevices are too large to be placed in many locations of the body.Therefore, the implanted devices require the use of long leads, whichcan be displaced or break. Such implanted devices are also implanted tostimulate upstream nerves, such as the vagus nerve, which leads tosignificant side effects due off target electrical stimulation.

There continues to be a need for implantable devices that can stimulatespecific nerves in a controlled manner and with limited risks and sideeffects.

The disclosures of all publications, patents, and patent applicationsreferred to herein are each hereby incorporated by reference in theirentireties. To the extent that any reference incorporated by referenceconflicts with the instant disclosure, the instant disclosure shallcontrol.

SUMMARY OF THE INVENTION

Described herein is an implantable medical device, comprising (a) a bodycomprising an ultrasonic transducer configured to receive ultrasonicwaves and convert energy from the ultrasonic waves into an electricalenergy that powers the device; (b) two or more electrodes in electricalcommunication with the ultrasonic transducer; and (c) a clip attached tothe body that is configured to at least partially surround a nerve andposition the two or more electrodes in electrical communication with thenerve. In some embodiments, the clip is configured to at least partiallysurround the nerve and a filamentous tissue attached to the nerve. Insome embodiments, the filamentous tissue is a blood vessel.

In some embodiments of the implantable medical device, the clipcomprises a plurality of flexible legs that extend below the body. Insome embodiments, the implantable device comprises a hook or loopconfigured to maneuver at least one of the flexible legs in response tomaneuvering the hook or loop. In some embodiments, the hook or loop ispositioned at a terminus of one of the flexible legs. In someembodiments, the hook or loop is positioned proximal to the body.

In some embodiments of the implantable medical device, the flexible legsare curved. In some embodiments, the legs extend away from the bodybefore curving toward the body as the legs extend below the body.

In some embodiments of the implantable medical device, the plurality offlexible legs comprises at least one pair of legs, wherein the pair oflegs comprises a first leg and a second leg that extend away from andbelow the body in opposite directions. In some embodiments, the firstleg and the second leg are connected by a crossbar connected to thebody. In some embodiments, the crossbar is connected to the body of thedevice through a flexible member. In some embodiments, the flexiblemember is a hinge. In some embodiments, the device comprises two pairsof legs, wherein each pair of leg is positioned on opposite sides of thebody. In some embodiments, the legs are attached to the body through abottom surface of the body. In some embodiments, the legs are attachedto the body through a sidewall of the body.

In some embodiments of the implantable medical device, the legs comprisea metal, metal alloy, ceramic, silicon, or a non-polymeric material. Insome embodiments, the legs comprise an elastomeric coating or anon-elastomeric polymer coating. In some embodiments, the coating isbioinert. In some embodiments, the coating is a silicone, apoly(p-xylylene) polymer, or a polyimide. In some embodiments, at leastone of the legs comprises an outer surface coated with the elastomericcoating or the non-elastomeric polymer coating and an inner surfacecomprising at least one electrode that is not coated with theelastomeric coating or the non-elastomeric polymer coating.

In some embodiments of the implantable medical device, the bodycomprises a bottom surface, and the two or more electrodes are terminateon the bottom of the body. In some embodiments, the two or moreelectrodes are positioned on the clip. In some embodiments, the clipcomprises a plurality of flexible legs that extend below the body, andthe two or more electrodes are positioned on the flexible legs.

In some embodiments of the implantable medical device, the bodycomprises a housing. In some embodiments, the housing comprises or iscoated with a bioinert material. In some embodiments, the housingcomprises the bioinert material, and wherein the bioinert material ofthe housing comprises titanium or a ceramic.

In some embodiments of the implantable medical device, the bodycomprises an integrated circuit electrically connected to the ultrasonictransducer and the two or more electrodes. In some embodiments, theintegrated circuit comprises an energy storage circuit comprising acapacitor.

In some embodiments of the implantable medical device, the body is about5 mm or less in length in the longest dimension.

In some embodiments of the implantable medical device, the ultrasonictransducer is configured to emit an ultrasonic backscatter that encodesdata. In some embodiments, the data comprises information related to adetected neural activity, a measured physiological condition, a devicestatus, or an emitted electrical pulse.

In some embodiments of the implantable medical device, the implantablemedical device is configured to emit an electrical pulse to the nerve.

In some embodiments of the implantable medical device, the ultrasonictransducer is configured to receive ultrasonic waves that encodeinstructions for operating the implantable device. In some embodiments,the instructions comprise a trigger signal that operates the implantabledevice to emit an electrical pulse to the nerve.

Also described herein is a method of implanting a medical device in asubject, the device comprising a body comprising an ultrasonictransducer configured to receive ultrasonic waves and convert energyfrom the ultrasonic waves into an electrical energy that powers thedevice, electrodes in electrical communication with the ultrasonictransducer, and a clip attached to the body, wherein the clip comprisesa plurality of flexible legs, the method comprising (a) outwardlyflexing one or more legs of the clip; (b) positioning the electrodes tobe in electrical communication with a nerve; and (c) releasing the oneor more legs of the clip, where the one or more legs at least partiallysurrounds the nerve and maintains the electrodes in electricalcommunication with the nerve upon release. In some embodiments, theplurality of legs at least partially surrounds the nerve and afilamentous tissue attached to the nerve. In some embodiments, thefilamentous tissue is a blood vessel. In some embodiments, the device islaparoscopically implanted in the subject. In some embodiments, the clipexerts an inward pressure on the nerve. In some embodiments, the clipallows for rotational movement around the nerve. In some embodiments,the legs exert a pressure on the nerve or the filamentous tissue ofabout 1 MPa or less.

In some embodiments of a method of implanting a medical device in asubject, the nerve is an autonomic nerve. In some embodiments, the nerveis a sympathetic nerve. In some embodiments, nerve is a mesentericnerve, a splenic nerve, a sciatic nerve, a tibial nerve, a celiacganglion, or a sacral nerve.

In some embodiments of a method of implanting the medical device in asubject, the plurality of legs extend below the body. In someembodiments, outwardly flexing one or more legs of the clip comprisesmaneuvering one or more hooks or loops connected to the one or morelegs. In some embodiments, the legs are curved. In some embodiments, thelegs extend away from the body before curving toward the body as thelegs extend below the body. In some embodiments, the plurality offlexible legs comprises at least one pair of legs, wherein the pair oflegs comprises a first leg and a second leg that extend away from andbelow the body in opposite directions. In some embodiments, the pair oflegs is connected by a crossbar connected to the body. In someembodiments, the crossbar is connected to the body of the device througha flexible member. In some embodiments, the flexible member is a hinge.In some embodiments, the device comprises two pairs of legs, whereineach pair of leg is positioned to opposite sides of the body. In someembodiments, the legs are attached to the body through a bottom surfaceof the body. In some embodiments, the legs are attached to the bodythrough a sidewall of the body. In some embodiments, the legs comprise ametal, metal alloy, ceramic, silicon, or a non-polymeric material. Insome embodiments, the legs comprise an elastomeric coating or anon-elastomeric polymer coating. In some embodiments, the coating isbioinert. In some embodiments, the coating is a silicone, a urethanepolymer, a poly(p-xylylene) polymer, or a polyimide. In someembodiments, at least one of the legs comprises an outer surface coatedwith the elastomeric coating or the non-elastomeric polymer coating andan inner surface comprising at least one electrode that is not coatedwith the elastomeric coating or the non-elastomeric polymer coating. Insome embodiments, the body comprises a bottom surface, and the two ormore electrodes are terminate on the bottom of the body. In someembodiments, the two or more electrodes are positioned on the clip. Insome embodiments, the clip comprises a plurality of flexible legs thatextend below the body, and the two or more electrodes are positioned onthe flexible legs.

In some embodiments of a method of implanting the medical device in asubject, the body comprises a housing. In some embodiments, the housingcomprises a bioinert material. In some embodiments, the housingcomprises the bioinert material, and wherein the bioinert material ofthe housing comprises titanium or a ceramic.

In some embodiments of a method of implanting the medical device in asubject, the body comprises an integrated circuit electrically connectedto the ultrasonic transducer and the two or more electrodes. In someembodiments, the integrated circuit comprises an energy storage circuitcomprising a capacitor. In some embodiments, the body is about 5 mm orless in length in the longest dimension.

Further described herein is an implantable medical device, comprising:(a) two or more ultrasonic transducers configured to receive ultrasonicwaves that power the device and emit an ultrasonic backscatter; (b) anintegrated circuit comprising an energy storage circuit comprising acapacitor, wherein the integrated circuit is electrically connected tothe first ultrasonic transducer and the second ultrasonic transducer;and (c) one or more of (i) a sensor configured to measure aphysiological condition, (ii) two or more electrodes configured to be inelectrical communication with a tissue and emit an electrical pulse tothe tissue, or (iii) two or more electrodes configured to be inelectrical communication with a tissue and detect anelectrophysiological signal from the tissue; wherein the sensor or thetwo or more electrodes are electrically connected to the integratedcircuit. In some embodiments, the two or more ultrasonic transducerscomprise a first ultrasonic transducer comprising a first polarizationaxis and a second ultrasonic transducer comprising a second polarizationaxis, wherein the second ultrasonic transducer is positioned so that thesecond polarization axis is orthogonal to the first polarization axis,and wherein the first ultrasonic transducer and the second ultrasonictransducer are configured to receive the ultrasonic waves that power thedevice and emit the ultrasonic backscatter.

In some embodiments, the implantable device comprises the sensorconfigured to measure a physiological condition. In some embodiments,the sensor is a temperature sensor, a pH sensor, a pressure sensor, astrain sensor, a pulse sensor, a blood pressure sensor, an oxygen meter,a glucose meter, an impedance meter, or is configured to measure ananalyte concentration.

In some embodiments, the implantable device comprises the two or moreelectrodes configured to be in electrical communication with a tissueand emit an electrical pulse to the tissue. In some embodiments, theimplantable device comprises the two or more electrodes configured to bein electrical communication with a tissue and detect anelectrophysiological signal from the tissue. In some embodiments, theelectrophysiological signal is a neural signal. In some embodiments, theultrasonic backscatter encodes information related to the measuredphysiological condition, the emitted electrical pulse, or the detectedelectrophysiological signal.

In some embodiments, the first ultrasonic transducer and the secondultrasonic transducer are electrically connected to the integratedcircuit in parallel. In some embodiments, the first ultrasonictransducer, the second ultrasonic transducer, and the integrated circuitare contained within a body, the device further comprising a clipconfigured to at least partially surround a filamentous tissue. In someembodiments, the filamentous tissue comprises a nerve. In someembodiments, the filamentous tissue comprises a nerve attached to ablood vessel. In some embodiments, the clip comprises a plurality offlexible legs that extend below the body.

In some embodiments of any of the implantable medical devices describedabove, the implantable medical device does not comprise a battery.

In some embodiments of any of the implantable medical devices describedabove, the implantable medical device does not comprise a radiofrequencycommunication system.

In some embodiments of any of the implantable medical devices describedabove, the implanted medical device does not comprise an electrical leadthat extends from the body of the device without terminating on a leg ofa clip.

Further provided herein, a system comprises any one of the implantablemedical devices described above, and an interrogator comprising one ormore ultrasonic transducers configured to transmit ultrasonic waves tothe implantable medical device, wherein the ultrasonic waves power theimplantable medical device. In some embodiments, the interrogator isconfigured to be worn externally. In some embodiments, the interrogatoris configured to receive ultrasonic backscatter emitted by theimplantable device, wherein the ultrasonic backscatter encodes data. Insome embodiments, the interrogator is configured to analyze the data ortransmit the data to a computer system. In some embodiments, theultrasonic waves transmitted by the interrogator encode instructions foroperating the implantable device.

Also described herein is a method of treating incontinence in a subject,comprising: converting energy from ultrasonic waves into electricalenergy that powers a fully implanted medical device in the subject, thedevice comprising two or more electrodes in electrical communicationwith a tibial nerve or a branch thereof, a pudendal nerve or a branchthereof, or a sacral nerve or a branch thereof of the subject; andelectrically stimulating the tibial nerve or the branch thereof, thepudendal nerve or the branch thereof, or the sacral nerve or the branchthereof, of the subject using the fully implanted medical device. Insome embodiments, the tibial nerve or the branch thereof, the pudendalnerve or the branch thereof, or the sacral nerve or the branch thereofis stimulated by the fully implanted medical device in response to atrigger signal encoded in the ultrasonic waves. In some embodiments,electrically stimulating the tibial nerve or the branch thereof, thepudendal nerve or the branch thereof, or the sacral nerve or the branchthereof comprises emitting a plurality of current pulses to the tibialnerve or the branch thereof, the pudendal nerve or the branch thereof,or the sacral nerve or the branch thereof. In some embodiments,electrically stimulating the tibial nerve or the branch thereof, thepudendal nerve or the branch thereof, or the sacral nerve or the branchthereof, comprises emitting a plurality of voltage pulses to the tibialnerve or the branch thereof, the pudendal nerve or the branch thereof,or the sacral nerve or the branch thereof.

In some embodiments of treating incontinence in a subject, the pluralityor current pulses or the plurality of voltage pulses are emitted at aconstant frequency. In some embodiments, the frequency of the pluralityof current pulses or the plurality of voltage pulses is between about 1Hz and about 50 Hz. In some embodiments, the method comprisestransmitting the ultrasonic waves to the implanted medical device usinga interrogator comprising one or more ultrasonic transducers. In someembodiments, the ultrasonic waves encode instructions for operating theimplantable device.

In some embodiments, the method comprises emitting an ultrasonicbackscatter that encodes data. In some embodiments, the data comprises astimulation status that indicates whether the implantable device emittedan electrical pulse or what parameters were used to emit the electricalpulse. In some embodiments, the method comprises receiving theultrasonic backscatter. In some embodiments, the method comprisesanalyzing the data encoded by the ultrasonic backscatter.

In some embodiments of treating incontinence, the interrogator is anexternally worn device. In some embodiments, the interrogator contactsthe skin of the subject. In some embodiments, the interrogator isoperated using a handheld device. In some embodiments, the handhelddevice is wirelessly connected to the interrogator.

In some embodiments of treating incontinence, the method comprisesimplanting the medical device in the subject to contact the two or moreelectrodes to the tibial nerve or the branch thereof, the pudendal nerveor the branch thereof, or the sacral nerve or the branch thereof.

In some embodiments of treating incontinence, the two or more electrodesare in electrical communication with the tibial nerve or the branchthereof. In some embodiments, the interrogator is attached to the ankleof the subject.

In some embodiments of treating incontinence, the two or more electrodesare in electrical communication with the sacral nerve or the branchthereof. In some embodiments, the interrogator is attached the hip,abdomen, lower back, buttocks, or upper leg of the patient.

In some embodiments of treating incontinence, the incontinence is anoveractive bladder, an underactive bladder, urinary incontinence, orfecal incontinence.

In some embodiments of treating incontinence, the subject is a human.

In some embodiments of treating incontinence, the implantable device isthe implantable medical device is any one of the implantable medicaldevices described above.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a side view of a body of an implantable device. The bodyincludes an ultrasonic transducer electrically connected to anintegrated circuit that includes a power circuit with a capacitor. Thebody further includes a bottom surface comprising feedthroughs, whichallow the integrated circuit to electrically connect with electrodespositioned elsewhere on the device.

FIG. 2 shows a top view of a body of an implantable device, including anultrasonic transducer, an integrated circuit, and a capacitor.

FIG. 3 shows an exemplary implantable device that includes an ultrasonictransducer, an integrated circuit and a sensor, which can be configuredto measure a physiological condition.

FIG. 4 shows a body of an implantable device that includes twoorthogonally positioned ultrasonic transducers. The body furtherincludes an integrated circuit that has a power circuit, which includesa capacitor.

FIG. 5 shows an exemplary implantable device with a body attached to aclip. The body includes an ultrasonic transducer and an integratedcircuit, which are electrically connected to electrodes that are inelectrical communication with a nerve. The clip holds the body to thenerve and the electrodes in position to electrically stimulate or detectan electrophysiological pulse from a nerve.

FIG. 6 shows another example of an implantable device that includes abody with a housing that encloses an ultrasonic transduce and anintegrated circuit. The body is attached to a clip that includes legsconfigured to at least partially surround a nerve and positionelectrodes in electrical communication with the nerve.

FIG. 7 shows a side view of another embodiment of an implantable devicewith a body attached to a clip having a plurality of legs. The clip isattached to the body underneath the bottom surface of the body. The legsare coated with a coating (which may be an elastomeric coating or anon-elastomeric polymer coating) on the outer surface of the legs, butare uncoated on the inner surface of the legs. The electrodes areuncoated and positioned on the inner surface of the legs.

FIG. 8A and FIG. 8B illustrate two exemplary configurations of legshaving electrodes positioned on the legs. In FIG. 8A, the leg includes asingle electrode that is positioned along the inner surface of the leg.In FIG. 8B, the leg includes a plurality of electrodes that terminate atdifferent positions along the inner surface of the leg.

FIG. 9A shows one embodiment of a leg with a hook at the terminus of theleg. FIG. 9B shows an embodiment of an implantable device with a hookproximal to the body of the device. The hook on the device in FIG. 9B isconnected to a leg on the opposite side of the body, and maneuvering thehook allows the leg to be flexed outwardly.

FIG. 10 shows an exemplary interrogator that can be used with theimplantable device.

FIG. 11 shows an interrogator in communication with an implantabledevice. The interrogator can transmit ultrasonic waves, which can encodea trigger signal. The implantable device emits an ultrasonicbackscatter, which can be modulated by the implantable device to encodeinformation.

FIG. 12 shows a schematic of one embodiment of an implantable deviceshowing the ultrasonic transducer and electrodes electrically connectedto an integrated circuit. The integrated circuit includes a powercircuit, which includes a capacitor that can store electrical energyfrom the ultrasonic transducer. The integrated circuit further includesa digital circuit or a multi-signal integrated circuit, which canoperate the power circuit and modulate an electrical current flowingthrough the ultrasonic transducer to encode information.

FIG. 13A shows an implantable device with a body and a clip fullyimplanted in a subject, wherein the clip attaches the implantable deviceto the tibial nerve. FIG. 13B shows an interrogator worn by a subjectthat can communicate with the implantable device in electricalcommunication with the tibial nerve.

FIG. 14 shows a system that includes an implantable device clipped to asacral nerve and an interrogator being used for sacral nerve stimulation(SNS). The implantable device includes a body having an ultrasonictransducer, electrodes, and a clip. The interrogator is optionallycontrolled by a mobile device, such as a smartphone or tablet.

DETAILED DESCRIPTION

Small, implantable devices that can detect electrophysiological signalsor a physiological condition, or emit electrical pulse to a nerve, aredescribed herein. The implantable devices are powered by ultrasonicwaves emitted by an external interrogator, which are received by anultrasonic transducer on the implantable device and converted intoelectrical energy. The ultrasonic waves emitted by the interrogator canfurther encode instructions for operating the implantable device, whichare received by the ultrasonic transducer on the implantable device. Theultrasonic waves transmitted by the external transducer can encode, forexample, a trigger signal that can signal the implantable device to emitan electrical pulse. In some embodiments, the implantable device emitsultrasonic backscatter waves, which may be received by the interrogatoror other external ultrasonic receiver. The ultrasonic backscatter wavescan encode data, such as data related to an electrical pulse (e.g.,neural activity) detected by the implantable device, a measuredphysiological condition, information related to an emitted electricalpulse, or information related to the status of the implantable medicaldevice.

The implantable device can include electrodes for stimulating nerves ordetecting neural activity. Because the implantable devices can beimplanted in mobile patients, there is a need to ensure the electrodesof the implantable device remain in electrical communication with thetarget nerve, as movement of the patient can cause shifting of internaltissues. As further described herein, an implantable device can includetwo or more electrodes, which can be configured to detect anelectrophysiological signal or emit an electrical pulse, and a clip thatis configured to at least partially surround a nerve and position thetwo or electrodes in electrical communication with the nerve. In somelocations of the body, the target nerve may be attached to anotherfilamentous tissue, such as a blood vessel. Accordingly, in someembodiments, the clip can be configured to at least partially surroundthe filamentous tissue or blood vessel. By using the clip to positionand retain the electrodes in place, there is no need to suture theimplantable device to tissue, which facilitates implantation and avoidssurrounding tissue damage. For example, the implantable device can nowbe laparoscopically implanted while ensuring the electrodes arecorrectly position during use.

Since the implantable device can move relative to the externalinterrogator, for example due to movement of the target nerve orrepositioning of the external interrogator, an implantable device with asingle ultrasonic transducer may have a weakened connection to theinterrogator if the polarization axis of the ultrasonic transducer ofthe implantable device becomes unaligned with the polarization axis ofthe one or more ultrasonic transducers of the interrogator. Accordingly,as further described herein, an implantable device can include two ormore ultrasonic transducers with non-parallel polarization axes. Forexample, in some embodiments, there is an implantable device with afirst ultrasonic transducer comprising a first polarization axis and asecond ultrasonic transducer comprising second polarization axis,wherein the second ultrasonic transducer is positioned so that thesecond polarization axis is orthogonal to the first polarization axis.In this configuration, ultrasonic waves emitted by the externaltransducer can be received by the implantable device positioned indifferent orientations to allow for continued powering of theimplantable device.

The implantable devices described herein may be used to stimulate anerve to treat a medical condition. Because the implantable devices aresmall, they can be implanted in a subject with limited invasiveness.Additionally, the implantable device can target nerves that are notpractically targeted with larger devices and without leads implanted inthe body that are connected externally. For example, the implantabledevices may be used to treat incontinence in a subject, for example byelectrically stimulating a tibial nerve, a pudendal nerve, or a sacralnerve, or a branch thereof using the fully implanted medical devicedescribed herein.

Definitions

As used herein, the singular forms “a,” “an,” and “the” include theplural reference unless the context clearly dictates otherwise.

Reference to “about” or “approximately” a value or parameter hereinincludes (and describes) variations that are directed to that value orparameter per se. For example, description referring to “about X”includes description of “X.”

It is understood that aspects and variations of the invention describedherein include “consisting” and/or “consisting essentially of” aspectsand variations.

The term “subject” and “patient” are used interchangeably herein torefer to a vertebrate animal.

The terms “treat,” “treating,” and “treatment” are used synonymouslyherein to refer to any action providing a benefit to a subject afflictedwith a disease state or condition, including improvement in thecondition through lessening, inhibition, suppression, or elimination ofat least one symptom, delay in progression of the disease or condition,delay in recurrence of the disease or condition, or inhibition of thedisease or condition.

Where a range of values is provided, it is to be understood that eachintervening value between the upper and lower limit of that range, andany other stated or intervening value in that stated range, isencompassed within the scope of the present disclosure. Where the statedrange includes upper or lower limits, ranges excluding either of thoseincluded limits are also included in the present disclosure.

It is to be understood that one, some or all of the properties of thevarious embodiments described herein may be combined to form otherembodiments of the present invention. The section headings used hereinare for organizational purposes only and are not to be construed aslimiting the subject matter described.

Features and preferences described above in relation to “embodiments”are distinct preferences and are not limited only to that particularembodiment; they may be freely combined with features from otherembodiments, where technically feasible, and may form preferredcombinations of features. The description is presented to enable one ofordinary skill in the art to make and use the invention and is providedin the context of a patent application and its requirements. Variousmodifications to the described embodiments will be readily apparent tothose persons skilled in the art and the generic principles herein maybe applied to other embodiments. Thus, the present invention is notintended to be limited to the embodiment shown but is to be accorded thewidest scope consistent with the principles and features describedherein.

Implantable Device

The implantable device includes a body, which contains one or moreultrasonic transducers and an integrated circuit that operates thedevice. The ultrasonic transducer receives ultrasonic waves, andconverts the received ultrasonic waves into an electrical energy thatpowers the device. The body of the device can include or be connected totwo or more electrodes or a sensor, which are in electric communicationwith the ultrasonic transducer (e.g., through the integrated circuit).In some embodiments, an electric current that flows through theultrasonic transducer can be modulated to encode information inultrasonic backscatter waves emitted by the ultrasonic transducer. Theinformation encoded in the ultrasonic backscatter waves may include, forexample, data related to a physiological condition detected by thesensor, an electrophysiological signal detected by the electrodes, astatus of the device (for example, a status confirming the device isreceiving signals encoded in ultrasonic waves, confirming operation ofthe integrated circuit, or confirming that the device is being powered),or information related to an electrical pulse emitted by the implantabledevice. In some embodiments, the implantable device comprises a clipattached to the body that is configured to at least partially surround anerve and position the two or more electrodes in electricalcommunication with the nerve. In some embodiments, the implantabledevice comprises a first ultrasonic transducer comprising a firstpolarization axis and a second ultrasonic transducer comprising secondpolarization axis, wherein the second ultrasonic transducer ispositioned so that the second polarization axis is orthogonal to thefirst polarization axis, and wherein the first ultrasonic transducer andthe second ultrasonic transducer are configured to receive ultrasonicwaves that power the device and emit an ultrasonic backscatter.

In some embodiments, the implantable device is implanted in a subject.The subject can be for example, a mammal. In some embodiments, thesubject is a human, dog, cat, horse, cow, pig, sheep, goat, monkey, or arodent (such as a rat or mouse).

Body of the Implantable Device

The body of the implantable device includes one or more ultrasonictransducers, and a sensor and/or an electrode pair. The electrode paircan be configured to detect an electrophysiological signal or emit anelectrical pulse. Exemplary implantable devices that can detect anelectrophysiological signal and encode information related to thedetected electrophysiological signal are described in WO 2018/009910 A2.Exemplary implantable devices that can be operated using ultrasonicwaves to emit an electrical pulse are described in WO 2018/009912 A2.The sensor may be, for example, sensor the can detect or measure aphysiological condition (such as temperature sensor, an oxygen sensor, apH sensor, a strain sensor, a pressure sensor, an impedance sensor, or asensor that can detect a concentration of an analyte). Exemplaryimplantable devices that are powered by ultrasonic waves and can emit anultrasonic backscatter encoding a detected physiological condition aredescribed in WO 2018/009905 A2 and WO 2018/009911 A2. In someembodiments, the implantable device comprises both a sensor and anelectrode pair. In some embodiments, an integrated circuit is includedin the implantable device, which can electrically connect andcommunicate between the electrodes or sensor and the ultrasonictransducer. The integrated circuit can include a modulation circuit,which modulates an electrical current flowing through the one or moreultrasonic transducers to encode data in the electrical current. Themodulated electrical current affects ultrasonic backscatter wavesemitted by the ultrasonic transducer, and the ultrasonic backscatterwaves encode the data.

FIG. 1 shows a side view of an exemplary implantable device body with anultrasonic transducer 102 and an integrated circuit 104. In theillustrated embodiment, the integrated circuit 104 includes a powercircuit that includes a capacitor 106. The capacitor can temporarilystore electrical energy converted from ultrasonic energy by theultrasonic transducer, and can be operated by the integrated circuit 104to store or release energy. The ultrasonic transducer 102, integratedcircuit 104, and the capacitor 106 are mounted on a backplate 108, whichmay be a printed circuit board. The base 108 is set in a housing, whichincludes a bottom surface 110 and sidewalls 112 a and 112 b. The housingcan further include a top (not shown) that seals the body components inthe housing. The bottom surface 110 may include one or more feedthroughs114 a, 114 b, and 114 c that electrically connect the backplate and/orintegrated circuit to one or more electrodes. The one or more electrodesmay be located, for example, underneath the bottom surface 110 of thehousing, or may be located on a clip as described herein. In thisconfiguration, the electrodes can be in electrical communication withthe nerve, and the components of the body are positioned above the nervewhen the implantable device is implanted and attached to the nerve, forexample using the clip as discussed herein. The ultrasonic transducer102 is electrically connected to the integrated circuit 104, and theintegrated circuit 104 is electrically connected to the electrodes viathe feedthroughs, thereby electrically connecting the ultrasonictransducer 102 to the electrodes.

FIG. 2 illustrates a top view of the body similar to the one shown inFIG. 1 , again without the top of the housing. The housing is shown withfour sidewalls 112 a, 112 b, 112 c, and 112 d, although it is understoodthat the housing can be of any suitable shape (e.g., with three, four,five, six or more sidewalls, or with a single curved sidewall in a roundor oval shape).

FIG. 3 illustrates a schematic of an exemplary implantable device withan ultrasonic transducer 302, and integrated circuit 304, and a sensor306 (such as sensor that can detect a temperature, pressure, strain,analyte concentration, oxygen, or pH). The ultrasonic transducer 302 iselectrically connected to the integrated circuit 304, which hiselectrically connected to the sensor 306. Although the illustratedembodiment is shown with an integrated circuit, it is also conceivedthat the sensor can be directly connected to the ultrasonic transducer.Further, as discussed herein, one or more sensor can be included on animplantable device further having electrodes configured to detect and/oremit an electrical pulse.

The ultrasonic transducer is configured to receive ultrasonic waves andconvert energy from the ultrasonic waves into an electrical energy. Theelectrical energy is transmitted to the integrated circuit to power thedevice. The implantable device can also operate to receive or transmitdata through ultrasonic waves. Ultrasonic waves received by theimplantable device (for example, those transmitted by the interrogator)can encode instructions for operating the implantable device. Theinstructions may include, for example, a trigger signal that instructsthe implantable device to emit an electrical pulse through theelectrodes. The trigger signal may include, for example, informationrelating to when the electrical pulse should be emitted, a pulsefrequency, a pulse power or voltage, a pulse shape, and/or a pulseduration

The implantable device can also operate to transmit data, which can bereceived by the interrogator. The ultrasonic transducer(s) on theimplantable device receive ultrasonic waves and emit an ultrasonicbackscatter, which can encode data transmitted by the implantabledevice. Current flows through the ultrasonic transducer, which can bemodulated to encode the data. The current may be modulated directly, forexample by passing the current through a sensor that modulates thecurrent, or indirectly, for example by modulating the current using amodulation circuit based on a detected physiological condition or anelectrophysiological pulse. In some embodiments, the data encoded in theultrasonic waves includes data unrelated to a detected physiologicalcondition or electrophysiological pules detected by the implantabledevice. For example, the data can include information related to thestatus of the implantable device or a confirmation signal that confirmsan electrical pulse was emitted, and optionally the power, frequency,voltage, duration, or other information related to an emitted electricalpulse.

In some embodiments, the body includes a housing, which can include abase, one or more sidewalls, and a top. The housing can enclose the oneor more ultrasonic transducers and the integrated circuit. The hosingmay be sealed closed (for example by soldering or laser welding) toprevent interstitial fluid from coming in contact with the ultrasonictransducer(s) and/or the integrated circuit. The electrodes that areconfigured to be in electrical communication with the nerve are notenclosed by the housing. The housing is preferably made from a bioinertmaterial, such as a bioinert metal (e.g., steel or titanium) or abioinert ceramic (e.g., titania or alumina). The housing (or the top ofthe housing) may be thin to allow ultrasonic waves to penetrate throughthe housing. In some embodiments, the thickness of the housing is about100 micrometers (μm) or less in thickness, such as about 75 μm or less,about 50 μm or less, about 25 μm or less, or about 10 μm or less. Insome embodiments, the thickness of the housing is about 5 μm to about 10μm, about 10 μm to about 25 μm, about 25 μm to about 50 μm, about 50 μmto about 75 μm, or about 75 μm to about 100 μm in thickness.

In some embodiments, the body comprises a material, such as a polymer,within the housing. The material can fill empty space within the housingto reduce acoustic impedance mismatch between the tissue outside of thehousing and within the housing. Accordingly, the body of the device ispreferably void of air or vacuum.

The body of the implantable device is relatively small, which allows forcomfortable and long-term implantation while limiting tissueinflammation that is often associated with implantable devices. In someembodiments, the longest dimension of the body of the device is about 5mm or less, about 4 mm or less, about 3 mm or less, about 2 mm or less,about 1 mm or less, about 0.5 mm or less, about 0.3 mm or less, about0.1 mm or less in length. In some embodiments, the longest dimension ofthe body of the device is about 0.05 mm or longer, about 0.1 mm orlonger, about 0.3 mm or longer, about 0.5 mm or longer, about 1 mm orlonger, about 2 mm or longer, or about 3 mm or longer in the longestdimension of the device. In some embodiments, the longest dimension ofthe body of the device is about 0.04 mm to about 5 mm in length, about0.05 mm to about 4 mm in length, about 0.07 mm to about 3 mm in length,about 0.08 mm to about 3 mm in length, or about 1 mm to about 2 mm inlength.

In some embodiments, the body of the implantable device has a volume ofabout 5 mm³ or less (such as about 4 mm³ or less, 3 mm³ or less, 2 mm³or less, or 1 mm³ or less). In some embodiments, the body of theimplantable device has a volume of about 0.5 mm³ to about 5 mm³, about 1mm³ to about 5 mm³, about 2 mm³ to about 5 mm³, about 3 mm³ to about 5mm³, or about 4 mm³ to about 5 mm³. The small size of the implantabledevice allows for laparoscopic implantation of the device, therebyminimizing tissue damage when implanting the device.

The implantable device includes one or more ultrasonic transducers, suchas one, two, or three or more ultrasonic transducers. In someembodiments, the implantable device includes a first ultrasonictransducer having a first polarization axis and a second ultrasonictransducer having a second polarization axis, wherein the secondultrasonic transducer is positioned so that the second polarization axisis orthogonal to the first polarization axis, and wherein the firstultrasonic transducer and the second ultrasonic transducer areconfigured to receive ultrasonic waves that power the device and emit anultrasonic backscatter. In some embodiments, the implantable medicaldevice includes a first ultrasonic transducer having a firstpolarization axis, a second ultrasonic transducer having a secondpolarization axis, and a third ultrasonic transducer having a thirdpolarization axis, wherein the second ultrasonic transducer ispositioned so that the second polarization axis is orthogonal to thefirst polarization axis and the third polarization axis, wherein thethird ultrasonic transducer is positioned so that the third polarizationaxis is orthogonal to the first polarization and the second polarizationaxis, and wherein the first ultrasonic transducer and the secondultrasonic transducer are configured to receive ultrasonic waves thatpower the device and emit an ultrasonic backscatter. An implantabledevice with one, two, or three or more ultrasonic transducers mayfurther include a sensor or two or more electrodes configured to be inelectrical communication with a tissue, such as a nerve. Optionally, theimplantable device further includes an integrated circuit.

FIG. 4 shows a body of a device that includes two orthogonallypositioned ultrasonic transducers. The body includes a backplate 402,such as a printed circuit board, and an integrated circuit 404, which apower circuit that includes a capacitor 406. The body further includes afirst ultrasonic transducer 408 electrically connected to the integratedcircuit 404, and a second ultrasonic transducer 410 electricallyconnected to the integrated circuit 404. The first ultrasonic transducer408 includes a first polarization axis 412, and the second ultrasonictransducer 410 includes a second polarization axis 414. The firstultrasonic transducer 408 and the second ultrasonic transducer arepositioned such that the first polarization axis 412 is orthogonal tothe second polarization axis 414. A housing (not shown) can enclose andoptionally seal the body components. Further, the integrated circuit canbe electrically coupled to a sensor or electrodes.

The ultrasonic transducer of the implantable device can be amicro-machined ultrasonic transducer, such as a capacitivemicro-machined ultrasonic transducer (CMUT) or a piezoelectricmicro-machined ultrasonic transducer (PMUT), or can be a bulkpiezoelectric transducer. Bulk piezoelectric transducers can be anynatural or synthetic material, such as a crystal, ceramic, or polymer.Exemplary bulk piezoelectric transducer materials include bariumtitanate (BaTiO₃), lead zirconate titanate (PZT), zinc oxide (ZO),aluminum nitride (AlN), quartz, berlinite (AIPO₄), topaz, langasite(La₃Ga₅SiO₁₄), gallium orthophosphate (GaPO₄), lithium niobate (LiNbO₃),lithium tantalite (LiTaO₃), potassium niobate (KNbO₃), sodium tungstate(Na₂WO₃), bismuth ferrite (BiFeO₃), polyvinylidene (di)fluoride (PVDF),and lead magnesium niobate-lead titanate (PMN-PT).

In some embodiments, the bulk piezoelectric transducer is approximatelycubic (i.e., an aspect ratio of about 1:1:1 (length:width:height). Insome embodiments, the piezoelectric transducer is plate-like, with anaspect ratio of about 5:5:1 or greater in either the length or widthaspect, such as about 7:5:1 or greater, or about 10:10:1 or greater. Insome embodiments, the bulk piezoelectric transducer is long and narrow,with an aspect ratio of about 3:1:1 or greater, and where the longestdimension is aligned to the direction of the ultrasonic backscatterwaves (i.e., the polarization axis). In some embodiments, one dimensionof the bulk piezoelectric transducer is equal to one half of thewavelength (λ) corresponding to the drive frequency or resonantfrequency of the transducer. At the resonant frequency, the ultrasoundwave impinging on either the face of the transducer will undergo a 180°phase shift to reach the opposite phase, causing the largestdisplacement between the two faces. In some embodiments, the height ofthe piezoelectric transducer is about 10 μm to about 1000 μm (such asabout 40 m to about 400 μm, about 100 μm to about 250 m, about 250 m toabout 500 μm, or about 500 μm to about 1000 μm). In some embodiments,the height of the piezoelectric transducer is about 5 mm or less (suchas about 4 mm or less, about 3 mm or less, about 2 mm or less, about 1mm or less, about 500 μm or less, about 400 μm or less, 250 μm or less,about 100 μm or less, or about 40 μm or less). In some embodiments, theheight of the piezoelectric transducer is about 20 μm or more (such asabout 40 μm or more, about 100 μm or more, about 250 μm or more, about400 μm or more, about 500 μm or more, about 1 mm or more, about 2 mm ormore, about 3 mm or more, or about 4 mm or more) in length.

In some embodiments, the ultrasonic transducer has a length of about 5mm or less such as about 4 mm or less, about 3 mm or less, about 2 mm orless, about 1 mm or less, about 500 μm or less, about 400 μm or less,250 μm or less, about 100 μm or less, or about 40 μm or less) in thelongest dimension. In some embodiments, the ultrasonic transducer has alength of about 20 μm or more (such as about 40 μm or more, about 100 μmor more, about 250 μm or more, about 400 μm or more, about 500 μm ormore, about 1 mm or more, about 2 mm or more, about 3 mm or more, orabout 4 mm or more) in the longest dimension.

The ultrasonic transducer is connected two electrodes to allowelectrical communication with the integrated circuit. The firstelectrode is attached to a first face of the transducer and the secondelectrode is attached to a second face of the transducer, wherein thefirst face and the second face are opposite sides of the transduceralong one dimension. In some embodiments, the electrodes comprisesilver, gold, platinum, platinum-black, poly(3,4-ethylenedioxythiophene(PEDOT), a conductive polymer (such as conductive PDMS or polyimide), ornickel. In some embodiments, the axis between the electrodes of thetransducer is orthogonal to the motion of the transducer.

In some embodiments, the implantable device includes two or moreelectrodes in electrical communication with a tissue, such as a nerve.The implantable device can include, for example, a clip as describedherein to position and retain the electrodes in electrical communicationwith the nerve. In some embodiments, an electrical pulse emitted by theimplantable device stimulates an action potential in the tissue. In someembodiments, an electrical pulse emitted by the implantable deviceblocks an action potential in a tissue.

In some embodiments, the implantable device comprises a plurality ofelectrodes. In some embodiments, the electrodes are paired. Electrodepairs can be formed from two electrodes' thus, an implantable devicewith three electrodes can have three electrode pairs. Theelectrophysiological signal can be detected between the electrodes inthe electrode pairs, or tissue can be stimulated using any of theelectrode pairs. In some embodiments, the implantable device comprises1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more, or 15 or more electrode pairs. Insome embodiments, the implantable device comprises 2, 3, 5, 6, 7, 8, 9,10 or more electrodes. In some embodiments, the implantable deviceincludes a multiplexer, which can select the electrodes in the electrodepair to emit the electrical pulse or the electrode pair that detects anelectrical pulse.

Two or more electrodes that are electrically connected to the nerve ortissue need not be linearly disposed along the tissue. For example, theelectrodes may engage a nerve or other tissue along a transverse axisrelative to the nerve, which can emit an electrical pulse in thetransverse direction. Two or more electrodes can engage a nerve or othertissue along the transverse axis at any angle, such as directly opposite(i.e., 180°), or less than 180° (such as about 170° or less, about 160°or less, about 150° or less, about 140° or less, about 130° or less,about 120° or less, about 110° or less, about 100° or less, about 90° orless, about 80° or less, about 70° or less, about 60° or less, about 50°or less, about 40° or less, or about 30° or less).

In some embodiments, the electrodes in an electrode pair are separatedby about 5 mm or less (such as about 4 mm or less, about 3 mm or less,about 2 mm or less, about 1.5 mm or less, about 1 mm or less, or about0.5 mm or less). In some embodiments, the electrodes in the electrodepair are separated by about 0.5 mm or more (such as about 1 mm or more,about 1.5 mm or more, about 2 mm or more, about 3 mm or more, or about 4or more. In some embodiments, the electrodes are separated by about 0.5mm to about 1 mm, about 1 mm to about 1.5 mm, about 1.5 mm to about 2mm, about 2 mm to about 3 mm, about 3 mm to about 4 mm, or about 4 mm toabout 5 mm.

The electrodes are electrically coupled to the integrated circuit in thebody of the implantable device. In some embodiments, the electrodes arepositioned or terminate below the body, for example on a face of thebase of the body housing opposite the body components (e.g., ultrasonictransducer, integrated circuit, etc.). In some embodiments, theelectrodes terminate along a leg of a clip, as detailed herein. In someembodiments, one or more electrodes are exposed along at least a portionof the length of one of the legs.

The electrodes may be electrically coupled to the integrated circuitthrough one or more feedthroughs in the base of the housing. Thefeedthroughs may be, for example, a metal (such as a metal comprisingsilver, copper, gold, platinum, platinum-black, or nickel) sapphire, ora conductive ceramic (for example indium tin oxide (ITO)). Theelectrodes may be connected to the feedthrough using any suitable means,such as soldering, laser welding, or crimping the feedthrough to theelectrodes.

In some embodiments, the implantable device includes one or moresensors. The sensors are configured to detect a physiological condition,such as temperature, oxygen concentration. pH, an analyte (such asglucose), strain, or pressure. Variation in the physiological conditionmodulates impedance, which in turn modulates current flowing through theultrasonic transducer on the implantable device. As explained above,this produces ultrasonic backscatter detected by the interrogator;changes in the ultrasonic backscatter waves reflect information aboutthe physiological condition. In some embodiments, the system isconfigured to detect changes in the physiological system. In someembodiments, the system is configured detect a value or an approximatevalue of the physiological condition, for example by calibrating theultrasonic backscatter to known values. The implantable device maycomprise one or more (such as 2, 3, 4, 5 or more) sensors, which maydetect the same physiological condition or different physiologicalconditions. In some embodiments, the implantable device comprises 10, 9,8, 7, 6 or 5 or fewer sensors). For example, in some embodiments, theimplantable device comprises a first sensor configured to detecttemperature and a second sensor configured to detect oxygen. Changes inboth physiological conditions can be encoded in the ultrasonicbackscatter waves, which can be deciphered by an external computingsystem.

The integrated circuit communicates between the ultrasonic transducerand the sensor and/or electrodes. For example, the ultrasonic transducercan receive information encoded in ultrasonic waves and generate anelectrical current that encodes the information, which is transmitted tothe integrated circuit. The information encoded in the electricalcurrent can include instructions to operate the electrodes and/orsensor, and the integrated circuit can operate the electrodes and/orsensor in accordance with the instructions. The integrated circuit canalso receive signals from the sensor and/or electrodes, and can modulatethe electrical current flowing through the ultrasonic transducer toencode information related to the signals received from the sensor andelectrodes.

In some embodiments, the implantable device emits ultrasonic backscatterthat encodes information. The ultrasonic backscatter can be received bythe interrogator, for example, and deciphered to determine the encodedinformation. The information can be encoded using a modulation circuitwithin the integrated circuit of the implantable device. The modulationcircuit can modulate the current flowing through the ultrasonictransducer to encode the information (e.g., information related to adetected electrophysiological pulse or a physiological condition, orinformation related to the device status). The modulated current flowsthrough the ultrasonic transducer to modulate the ultrasonicbackscatter, thereby encoding the information in the ultrasonicbackscatter waves. The modulation circuit includes one or more switches,such as an on/off switch or a field-effect transistor (FET). Anexemplary FET that can be used with some embodiments of the implantabledevice is a metal-oxide-semiconductor field-effect transistor (MOSFET).The modulation circuit can alter the impedance of a current flowingthrough the ultrasonic transducer, and variation in current flowingthrough the transducer encodes the electrophysiological signal. In someembodiments, information encoded in the ultrasonic backscatter includesa unique identifier for the implantable device. This can be useful, forexample, to ensure the interrogator is in communication with the correctimplantable device when a plurality of implantable devices is implantedin the subject. In some embodiments, the information encoded in theultrasonic backscatter includes a verification signal that verifies anelectrical pulse was emitted by the implantable device. In someembodiments, the information encoded in the ultrasonic backscatterincludes an amount of energy stored or a voltage in the energy storagecircuit (or one or more capacitors in the energy storage circuit). Insome embodiments, the information encoded in the ultrasonic backscatterincludes a detected impedance. Changes in the impedance measurement canidentify scarring tissue or degradation of the electrodes over time.

In some embodiments, the modulation circuit is operated by a digitalcircuit or a mixed-signal integrated circuit, which can actively encodethe information in a digitized or analog signal. The digital circuit ormixed-signal integrated circuit may include a memory and one or morecircuit blocks, systems, or processors for operating the implantabledevice. These systems can include, for example, an onboardmicrocontroller or processor, a finite state machine implementation, ordigital circuits capable of executing one or more programs stored on theimplant or provided via ultrasonic communication between interrogatorand implantable device. In some embodiments, the digital circuit or amixed-signal integrated circuit includes an analog-to-digital converter(ADC), which can convert analog signal encoded in the ultrasonic wavesemitted from the interrogator so that the signal can be processed by thedigital circuit or the mixed-signal integrated circuit. The digitalcircuit or mixed-signal integrated circuit can also operate the powercircuit, for example to generate the electrical pulse to stimulate thetissue. In some embodiments, the digital circuit or the mixed-signalintegrated circuit receives the trigger signal encoded in the ultrasonicwaves transmitted by the interrogator, and operates the power circuit todischarge the electrical pulse in response to the trigger signal.

In some embodiments, the integrated circuit includes a power circuit,which can include an energy storage circuit. The implantable devicepowered by ultrasonic waves is preferably batteryless, although theenergy storage circuit can include one or more capacitors to temporarilystore electrical energy. Energy from the ultrasonic waves is convertedinto a current by the ultrasonic transducer, and can be stored in theenergy storage circuit. The energy can be used to operate theimplantable device, such as providing power to the digital circuit, themodulation circuit, or one or more amplifiers, or can be used togenerate the electrical pulse used to stimulate the tissue. In someembodiments, the power circuit further includes, for example, arectifier and/or a charge pump.

In some embodiments, the integrated includes a driver circuit, whichprovides current to one or more sensors and/or electrodes. Optionally,the driver circuit is operated by the digital circuit or mixed-signalintegrated circuit if present. In some embodiments, one or moreamplifiers are disposed between the driver circuit and the digitalcircuit. In some embodiments, the integrated includes a front endcircuit (such as a CMOS front end), which can receive a signal from thesensor/and or electrodes. The signal received by the front end circuitcan be relayed to the digital circuit.

FIG. 12 shows a schematic an embodiment of an implantable device thatincludes an integrated circuit and electrodes configured to emit anelectrical pulse. The implantable device includes a ultrasonictransducer, a power circuit including an energy storage circuit (whichcan include one or more capacitors (“cap”), a digital circuit ormulti-signal integrated circuit, and a pair of electrodes. Theultrasonic transducer is connected to the power circuit, which allowsenergy from the ultrasonic waves to be stored in the energy storagecircuit. The power circuit is connected to the digital circuit ormulti-signal integrated circuit so that the digital circuit ormulti-signal integrated circuit can operate the power circuit. Thedigital circuit or multi-signal integrated circuit is also connected tothe ultrasonic transducer. When a trigger signal is encoded inultrasonic waves received by the ultrasonic transducer, the digitalcircuit or multi-signal integrated circuit can detect the triggersignal. The digital circuit or multi-signal integrated circuit can thenoperate the power circuit to release energy stored in the energycircuit, thereby emitting an electrical pulse using the electrodes.Optionally, the digital circuit or multi-signal integrated circuit canoperate or include a modulation circuit, which can modulate theelectrical current flowing through the ultrasonic transducer to encodeinformation, such as information relating to operation of theimplantable device or information related to an electrical pulsedetected by the electrodes.

Clip for the Implantable Device

In some embodiments, the implantable medical device includes a clipattached to the body that is configured to at least partially surround anerve to position the two or more electrodes in electrical communicationwith the nerve. Some nerves in the body may be attached to an adjacentfilamentous tissue (e.g., a blood vessel or tendon), and the clip can beconfigured to at least partially surround the nerve and the filamentoustissue.

The clip holds the implantable device in place on the nerve and/orfilamentous tissue. In some embodiments, the clip allows for somerotational movement of the implantable device on the nerve and/orfilamentous tissue. In some embodiments, the clip grips the nerve and/orfilamentous tissue by exerting an inward pressure on the nerve and/orfilamentous tissue. The amount of inward pressure exerted by the clipcan be determined based on the size and curvature of the clip, as wellas by the spring constant of the clip legs. The inward pressure shouldbe sufficient to hold the implantable device in place while the tissueheals after insertion, but not so high that the epineurium or vascularwalls that contact the legs are damaged. In some embodiments, the inwardpressure on the nerve or filamentous tissue is about 1 MPa or less (suchas about 0.7 MPa or less, about 0.5 MPa or less, or about 0.3 MPa orless). In some embodiments, the inward pressure on the nerve orfilamentous tissue is about 0.1 MPa to about 1 MPa (such as about 0.1MPa to about 0.3 MPa, about 0.3 MPa to about 0.5 MPa, about 0.5 MPa toabout 0.7 MPa, or about 0.7 MPa to about 1 MPa).

In some embodiments, the implantable medical device includes a bodycomprising an ultrasonic transducer configured to receive ultrasonicwaves and convert energy from the ultrasonic waves into an electricalenergy that powers the device; two or more electrodes in electricalcommunication with the ultrasonic transducer; and a clip attached to thebody that is configured to at least partially surround a nerve (or anerve and a filamentous tissue attached to the nerve, such as a bloodvessel) and position the two or more electrodes in electricalcommunication with the nerve.

The clip can include a plurality of flexible legs that extend below thebody of the implantable device. In some embodiments, the legs arecurved. For example, in some embodiments, the legs extend away from thebody before curving toward the body as the legs extend below the body.The clip may include pairs of legs, with each leg in the pair extendingaway from the body in opposite directions. This configuration allows thelegs to wrap around the nerve and/or filamentous tissue (or at leastpartially wrap around the nerve and/or filamentous tissue). The legs inthe pair of legs can be connected by a crossbar, which allows the legsto be positioned in a staggered configuration, with one the legs in thepair being positioned closer to the body than the other leg. Bystaggering the legs at different distances from the body of the device,the legs can extend such that the ends of the legs extend past eachother to completely surround the nerve and/or filamentous tissue. Insome embodiments, the legs in the pair of the legs and the crossbar area single piece (e.g., co-extruded or a co-printed) of material, such asa metal, metal alloy, ceramic, silicon, or a non-polymeric material. Thelegs or the crossbar(s) of the device are connected to the body of thedive. If the implantable device includes two pairs of legs eachconnected by a crossbar, the crossbars may be attached to the body atopposite ends of the body. The lengths of the crossbars attached to thebody can be along the same axis, which can be parallel to the axis ofthe nerve and/or filamentous tissue.

In some embodiments, the legs or the crossbar(s) of the implantabledevice are connected to the body of the device through a flexiblemember, such as a hinge (which may be a spring hinge). The flexibilityof the legs and flexible member allows the implantable device to bemaneuvered in position on the nerve by flexing the legs of the clip,which can return to their default position to correctly position theelectrodes of the device in electrical communication with the nerve.

FIG. 5 shows one example of an implantable device with a clip. Theimplantable device includes a body 502, which includes an ultrasonictransducer 504 and an integrated circuit 506. The ultrasonic transducer504 can receive ultrasonic waves from an interrogator, and theultrasonic transducer converts energy from the ultrasonic waves into anelectrical energy that powers the device. The ultrasonic transducer 504is electrically connected to the integrated circuit 506, which canencode data in an electric current that flows through the ultrasonictransducer 504. The ultrasonic transducer 504 emits an ultrasonicbackscatter based on the received current, and the ultrasonicbackscatter encodes the data that was encoded in the electric current.

The implantable device includes two or more electrodes that are inelectric communication with the ultrasonic transducer 504, for examplethrough the integrated circuit 506. In some configurations, theelectrodes are configured to emit an electrical pulse to the nerve, forexample by being operated by the integrated circuit 506. Optionally, anelectrophysiological pulse can be detected by the electrodes andcommunicated to the integrated circuit 506, which can modulate anelectric current flowing through the ultrasonic transducer 504 based onthe detected electrophysiological pulse. The body 502 of the implantabledevice is attached to a clip 508. The clip is configured to surround anerve 510 and position the two or more electrodes in electricalcommunication with the never. In the embodiment illustrated in FIG. 5 ,the electrodes are positioned along the bottom of the body 502 incontact with the nerve 510. In some embodiments, the two or moreelectrodes are in physical contact with the nerve, although somemovement of the implantable device may be allowed so long as theelectrodes remain in electrical communication with the nerve. Theelectrodes need not penetrate the epineurium of the nerve.

The clip includes a first leg 512 and a second leg 514, which arepositioned on opposite sides of the nerve 510. The legs of the clip areoptionally flexible so that the legs can be flexed outwardly to positionthe clip on the nerve. When the legs are released, the legs springinwardly to maintain the electrodes in electrical communication with thenerve. The size and spacing of the legs can be set depending on the sizeof the nerve. In embodiment illustrated in FIG. 5 , leg 514 has a widthapproximately the same length as the body 502. The leg 514 includes afirst segment 516 that extends from the body along the side of the nerve510 to below the nerve 510, and a second segment 518 that extends fromthe bottom of the first portion toward the underside of the nerve 510. Aflexible member 520 (such as a hinge, which may be a spring hinge) joinsthe first segment 516 and the second segment 518, which can allow thesecond segment 518 to flex toward the first segment 516 when theimplantable device is being positioned on the nerve. The end of secondsegment 518 can be released and the second segment 518 springs intoposition below the nerve 510. Optionally, a second flexible member 522(which may be, for example, a hinge, which may be a spring hinge)attaches the leg 508 to the body 502. The second flexible member 522allows the leg 514 to flex outwardly when positioning the implantabledevice on the nerve 510.

FIG. 6 shows another example of an implantable device, which includes abody 602 and a clip configured to at least partially surround a nerve,comprising a plurality of flexible legs 604, 606, 608, and 610. The body602 includes a housing, and contains an ultrasonic transducer configuredto receive ultrasonic waves and convert energy from the ultrasonic wavesinto an electrical energy that powers the implantable device. Theimplantable device further includes a plurality of electrodes positionedon the bottom of the body housing. The electrodes are in electricalcommunication with the ultrasonic transducer, for example through anintegrated circuit contained within the body 602 of the implantabledevice. When the clip is positioned on the nerve to at least partiallysurround the nerve, the electrodes are positioned to be in electricalcommunication with the nerve.

The legs 604, 606, 608, and 610 of the implantable device extend belowthe body 602 and are curved, which allows the legs to wrap around thenerve and any filamentous tissue (e.g., a blood vessel) that may beattached to the nerve. The upper portion of the legs extend away fromthe body 602, and the legs curve back toward the body 602 as they extendbelow the body. The clip illustrated in FIG. 6 includes a first pair oflegs, 604 and 606, and a second pair of legs 608 and 610. The pairedlegs extend away from the body in opposite directions. The upper portionof legs 604 and 606 are connected by crossbar 612, and the upper portionof legs 608 and 610 are connected by crossbar 614. Crossbar 612 isconnected to the body 602 through flexible member 616, and crossbar 614is connected to the body 602 through a second flexible member (notshown). The flexible member may be, for example, a hinge (which may be aspring hinge). The crossbars are connected to opposite sides of the body602, and the length of the crossbars are oriented in the same direction(i.e., parallel to the nerve).

The size and shape of the clip can depend on the type and size of tissuethat engages the clip. The clip is designed to allow the legs of theclip to at least partially surround filamentous tissue, such as a nerveor blood vessel. In some embodiments, such as the clip of the deviceshown in FIG. 6 , the inner surface of the legs form a cylindrical spacethrough which the nerve and/or filamentous tissue passes. The diameterof the cylindrical space formed by the legs depends on the target nerveand/or filamentous tissue that the implantable device will engage. Insome embodiments, the legs of the device form a cylindrical space with adiameter of about 50 μm to about 15 mm (for example, about 50 μm toabout 100 μm, about 100 m to about 250 μm, about 250 μm to about 500 μm,about 500 μm to about 1 mm, about 1 mm to about 1.5 mm, about 1.5 mm toabout 2.5 mm, about 2.5 mm to about 5 mm, about 5 mm to about 10 mm, orabout 10 mm to about 15 mm). For example, a clip designed to at leastpartially surround the splenic nerve of a human can include curved legsthat form a cylindrical space with a dimeter of about 500 μm to about1.5 mm. The legs of device may also be sized to optimally engage thenerve, and in some embodiments may have a width (including any coatingmaterial on the legs) of about 100 μm to about 4 mm (such as about 100μm to about 200 μm, about 200 μm to about 400 μm, about 400 μm to about1 mm, about 1 mm to about 2 mm, about 2 mm to about 3 mm, or about 3 mmto about 4 mm). In some embodiments, a clip designed to at leastpartially surround the splenic nerve of a human can include legs with awidth of about 200 μm to about 2 mm.

As some nerves may be attached to a filamentous tissue, such as a bloodvessel, the clip can be designed to at least partially surround thenerve and the filamentous tissue. In some embodiments, a clip configuredto at least partially surround a nerve attached to a filamentous tissue(such as a blood vessel) can include curved legs that form a cylindricalspace with a diameter of about 1 mm to about 10 mm (such as about 1 mmto about 2 mm, about 2 mm to about 3 mm, about 3 mm to about 4 mm, about4 mm to about 5 mm, about 5 mm to about 6 mm, about 6 mm to about 7 mm,about 7 mm to about 8 mm, about 8 mm to about 9 mm, or about 9 mm toabout 10 mm). For example, a clip configured to engage a splenic nerveattached to a splenic artery can include curved legs that form acylindrical space with a dimeter of about 2 mm to about 8 mm. The legsof device may also be sized to optimally engage the nerve and thefilamentous tissue (such as a blood vessel), and in some embodiments mayhave a width (including any coating material on the legs) of about 100μm to about 4 mm (such as about 100 μm to about 200 μm, about 200 μm toabout 400 μm, about 400 μm to about 1 mm, about 1 mm to about 2 mm,about 2 mm to about 3 mm, or about 3 mm to about 4 mm). In someembodiments, a clip designed to at least partially surround the splenicnerve and the splenic artery of a human can include legs with a width ofabout 500 μm to about 2 mm.

FIG. 7 shows a side view of another embodiment of an implantable devicewith a clip. Similar to the implantable device shown in FIG. 6 , theimplantable device includes a body 702 with a clip configured to atleast partially surround a nerve. The clip includes legs 704 and 706,although it is contemplated that the device optionally includesadditional legs and/or one or more crossbars. The bottom surface 708 ofthe housing 702 includes feedthroughs 710, 712, and 714. Thefeedthroughs electrically connect the integrated circuit in the body ofthe device to the electrodes. For example, feedthrough 710 iselectrically connected to electrode 716 through connection 718, andfeedthrough 714 is electrically connected to electrode 720 throughconnection 722. The connections 718 and 722 may be, for example, asolder, a weld, or a crimp connecting the feedthrough to the electrode.Electrode 716 is positioned on the internal surface of leg 704, andelectrode 720 is positioned on the internal surface of leg 706. Theelectrodes are in electrical communication with the ultrasonictransducer, for example through an integrated circuit contained withinthe body 702 of the implantable device via the feedthroughs. When theclip is positioned on the nerve to at least partially surround thenerve, the electrodes are positioned to be in electrical communicationwith the nerve. Leg 704 and leg 706 are secured to the body 702 of thedevice through a sealing material 724. The sealing material can alsoseal the connections 718 and 722. In some embodiments, the sealingmaterial is an epoxy or a polymer (such as silicone or a urethanepolymer).

The legs of the implantable device can comprise a metal, metal alloy,ceramic, silicon, or a non-polymeric material. In some embodiments, oneor more electrodes are positioned on an inner surface of the legs. Thelegs are flexible, and preferably sprung such that the legs can bepositioned around the nerve and/or filamentous tissue. In someembodiments, the legs or a portion of the legs are coated with anelastomeric coating or a non-elastomeric coating, which is preferablybioinert, such as polydimethylsioloxane (PDMS), a silicone, a urethanepolymer, a poly(p-xylylene)polymer (such as a poly(p-xylylene) polymersold under the tradename PARYLENE®), or a polyimide. In someembodiments, the implantable device includes one or more electrodes onthe inner surface of the legs. In some embodiments, one or more of theelectrodes on the inner surface of the legs are not coated with theelastomeric coating or the non-elastomeric polymer coating, although maybe coated with a conductive material (e.g., electroplated with a PEDOTpolymer or a metal to improve electrical characteristics of theelectrode). Accordingly, in some embodiments, only the outer surface ofthe legs is coated with the coating. Optionally, the coating furthercoats the housing of the body. Referring to FIG. 7 by way of example,the outer surface of legs 704 and 706 are coated with the coating 726.However, because electrodes 716 and 720 are on the inner surface of legs704 and 706, the coating 726 does not coat the inner surface of thelegs.

FIG. 8A and FIG. 8B illustrate two exemplary configurations withelectrodes on the legs of the clips. As shown in FIG. 8A, the leg 802 iscoated with a coating 804, such as an elastomeric polymer or anon-elastomeric polymer. A single electrode is exposed through theelastomeric or non-elastomeric polymer, which can be in electricalcommunication with a nerve. FIG. 8B illustrates a leg 806 with aplurality of electrodes 808 along the inner surface of the leg. In theembodiment illustrated in FIG. 8B, the leg 806 is not coated with anelastomeric polymer or a non-elastomeric polymer. However, the leg 806could be optionally coated with the polymer on the outer surface of theleg 806.

In some embodiments, the legs comprise one or more hooks or loops, whichmay be positioned proximal to the terminus of the legs or may bepositioned along the length of the leg. The hook or loop can be used tohelp manipulate, flex, or position the clip into position. In someembodiments, the hook or loop curves toward the body of the implantabledevice, and in some embodiments the hook or loop curves away from thebody of the implantable device. FIG. 9A shows one embodiment of a legwith a hook at the terminus of the leg. The leg 902 connects to the bodyof the device at the starting end 904, and extends below and away fromthe body. The leg 902 curves inwardly at 906 before curving outwardly at908 to form a hook 910 at the terminus 912 of the leg. In someembodiments, the clip includes a hook or a loop configured to manipulatea leg of the clip, for example as shown in FIG. 9B. The implantabledevice includes a body 914 attached to a leg 916 that extends below andaway from the body 914. The leg 916 is connected to a hook 918 oppositethe body 914, for example through a continuous member (for example,metal or non-elastomeric plastic). The hook 918 and the leg 916 may be,for example, co-extruded or co-printed to form the continuous member.When hook 918 is pushed downwardly, the leg 916 is pushed outwardly.Through this mechanism, the implantable device can be properlypositioned on a nerve, for example through laparoscopic implantation.

The two or more electrodes of the implantable device are positioned bythe clip to be in electrical communication with the nerve. In someembodiments, the two or more electrodes directly contact the nerve. Insome embodiments, the two or more electrodes are positioned within about2 mm (within about 1.8 mm, within about 1.6 mm, within about 1.4 mm,within about 1.2 mm, within about 1.0 mm, within about 0.8 mm, withinabout 0.6 mm, within about 0.4 mm, or within about 0.2 mm of the nerve.The electrodes may be disposed on the bottom of the body or on one ormore clip legs. Legs that extend below the body secure the body to thenerve, and by positioning the electrodes on the bottom of the body, theelectrodes are positioned in electrical communication with the nerve.

Interrogator

The interrogator can wirelessly communicate with one or more implantabledevices using ultrasonic waves, which are used to power and/or operatethe implantable device. For example, the interrogator can transmitultrasonic waves that encode instructions for operating the device, suchas a trigger signal that instructs the implantable device to emit anelectrical pulse. The interrogator can further receive ultrasonicbackscatter from the implantable device, which encodes informationtransmitted by the implantable device. The information may include, forexample, information related to a detected electrophysiological pulse,an electrical pulse emitted by the implantable device, and/or a measuredphysiological condition. The interrogator includes one or moreultrasonic transducers, which can operate as an ultrasonic transmitterand/or an ultrasonic receiver (or as a transceiver, which can beconfigured to alternatively transmit or receive the ultrasonic waves).The one or more transducers can be arranged as a transducer array, andthe interrogator can optionally include one or more transducer arrays.In some embodiments, the ultrasound transmitting function is separatedfrom the ultrasound receiving function on separate devices. That is,optionally, the interrogator comprises a first device that transmitsultrasonic waves to the implantable device, and a second device thatreceives ultrasonic backscatter from the implantable device. In someembodiments, the transducers in the array can have regular spacing,irregular spacing, or be sparsely placed. In some embodiments the arrayis flexible. In some embodiments the array is planar, and in someembodiments the array is non-planar.

An exemplary interrogator is shown in FIG. 10 . The illustratedinterrogator shows a transducer array with a plurality of ultrasonictransducers. In some embodiments, the transducer array includes 1 ormore, 2 or more, 3 or more, 5 or more, 7 or more, 10 or more, 15 ormore, 20 or more, 25 or more, 50 or more, 100 or more 250 or more, 500or more, 1000 or more, 2500 or more, 5000 or more, or 10,000 or moretransducers. In some embodiments, the transducer array includes 100,000or fewer, 50,000 or fewer, 25,000 or fewer, 10,000 or fewer, 5000 orfewer, 2500 or fewer, 1000 or fewer, 500 or fewer, 200 or fewer, 150 orfewer, 100 or fewer, 90 or fewer, 80 or fewer, 70 or fewer, 60 or fewer,50 or fewer, 40 or fewer, 30 or fewer, 25 or fewer, 20 or fewer, 15 orfewer, 10 or fewer, 7 or fewer or 5 or fewer transducers. The transducerarray can be, for example a chip comprising 50 or more ultrasonictransducer pixels.

The interrogator shown in FIG. 10 illustrates a single transducer array;however the interrogator can include 1 or more, 2 or more, or 3 or moreseparate arrays. In some embodiments, the interrogator includes 10 orfewer transducer arrays (such as 9, 8, 7, 6, 5, 4, 3, 2, or 1 transducerarrays). The separate arrays, for example, can be placed at differentpoints of a subject, and can communicate to the same or differentimplantable devices. In some embodiments, the arrays are located onopposite sides of an implantable device. The interrogator can include anapplication specific integrated circuit (ASIC), which includes a channelfor each transducer in the transducer array. In some embodiments, thechannel includes a switch (indicated in FIG. 10 by “T/Rx”). The switchcan alternatively configure the transducer connected to the channel totransmit ultrasonic waves or receive ultrasonic waves. The switch canisolate the ultrasound receiving circuit from the higher voltageultrasound transmitting circuit.

In some embodiments, the transducer connected to the channel isconfigured only to receive or only to transmit ultrasonic waves, and theswitch is optionally omitted from the channel. The channel can include adelay control, which operates to control the transmitted ultrasonicwaves. The delay control can control, for example, the phase shift, timedelay, pulse frequency and/or wave shape (including amplitude andwavelength). The delay control can be connected to a level shifter,which shifts input pulses from the delay control to a higher voltageused by the transducer to transmit the ultrasonic waves. In someembodiments, the data representing the wave shape and frequency for eachchannel can be stored in a ‘wave table’. This allows the transmitwaveform on each channel to be different. Then, delay control and levelshifters can be used to ‘stream’ out this data to the actual transmitsignals to the transducer array. In some embodiments, the transmitwaveform for each channel can be produced directly by a high-speedserial output of a microcontroller or other digital system and sent tothe transducer element through a level shifter or high-voltageamplifier. In some embodiments, the ASIC includes a charge pump(illustrated in FIG. 10 ) to convert a first voltage supplied to theASIC to a higher second voltage, which is applied to the channel. Thechannels can be controlled by a controller, such as a digitalcontroller, which operates the delay control.

In the ultrasound receiving circuit, the received ultrasonic waves areconverted to current by the transducers (set in a receiving mode), whichis transmitted to a data capture circuit. In some embodiments, anamplifier, an analog-to-digital converter (ADC), avariable-gain-amplifier, or a time-gain-controlledvariable-gain-amplifier which compensates for tissue loss, and/or a bandpass filter is included in the receiving circuit. The ASIC can drawpower from a power supply, such as a battery (which is preferred for awearable embodiment of the interrogator). In the embodiment illustratedin FIG. 10 , a 1.8V supply is provided to the ASIC, which is increasedby the charge pump to 32V, although any suitable voltage can be used. Insome embodiments, the interrogator includes a processor and or anon-transitory computer readable memory. In some embodiments, thechannel described above does not include a T/Rx switch but insteadcontains independent Tx (transmit) and Rx (receive) with a high-voltageRx (receiver circuit) in the form of a low noise amplifier with goodsaturation recovery. In some embodiments, the T/Rx circuit includes acirculator. In some embodiments, the transducer array contains moretransducer elements than processing channels in the interrogatortransmit/receive circuitry, with a multiplexer choosing different setsof transmitting elements for each pulse. For example, 64 transmitreceive channels connected via a 3:1 multiplexer to 192 physicaltransducer elements—with only 64 transducer elements active on a givenpulse.

In some embodiments, the interrogator is implantable. In someembodiments, the interrogator is external (i.e., not implanted). By wayof example, the external interrogator can be a wearable, which may befixed to the body by a strap or adhesive. In another example, theexternal interrogator can be a wand, which may be held by a user (suchas a healthcare professional). In some embodiments, the interrogator canbe held to the body via suture, simple surface tension, a clothing-basedfixation device such as a cloth wrap, a sleeve, an elastic band, or bysub-cutaneous fixation. The transducer or transducer array of theinterrogator may be positioned separately from the rest of thetransducer. For example, the transducer array can be fixed to the skinof a subject at a first location (such as proximal to one or moreimplanted devices), and the rest of the interrogator may be located at asecond location, with a wire tethering the transducer or transducerarray to the rest of the interrogator.

The specific design of the transducer array depends on the desiredpenetration depth, aperture size, and size of the individual transducerswithin the array. The Rayleigh distance, R. of the transducer array iscomputed as:

${R = {\frac{D^{2} - \lambda^{2}}{4\lambda} \approx \frac{D^{2}}{4\lambda}}},{D^{2} \gg \lambda^{2}}$where D is the size of the aperture and I is the wavelength ofultrasound in the propagation medium (i.e., the tissue). As understoodin the art, the Rayleigh distance is the distance at which the beamradiated by the array is fully formed. That is, the pressure filedconverges to a natural focus at the Rayleigh distance in order tomaximize the received power. Therefore, in some embodiments, theimplantable device is approximately the same distance from thetransducer array as the Rayleigh distance.

The individual transducers in a transducer array can be modulated tocontrol the Raleigh distance and the position of the beam of ultrasonicwaves emitted by the transducer array through a process of beamformingor beam steering. Techniques such as linearly constrained minimumvariance (LCMV) beamforming can be used to communicate a plurality ofimplantable devices with an external ultrasonic transceiver. See, forexample. Bertrand et al., Beamforming Approaches for Untethered,Ultrasonic Neural Dust Motes for Cortical Recording: a Simulation Study.IEEE EMBC (August 2014). In some embodiments, beam steering is performedby adjusting the power or phase of the ultrasonic waves emitted by thetransducers in an array.

In some embodiments, the interrogator includes one or more ofinstructions for beam steering ultrasonic waves using one or moretransducers, instructions for determining the relative location of oneor more implantable devices, instructions for monitoring the relativemovement of one or more implantable devices, instructions for recordingthe relative movement of one or more implantable devices, andinstructions for deconvoluting backscatter from a plurality ofimplantable devices.

Optionally, the interrogator is controlled using a separate computersystem, such as a mobile device (e.g., a smartphone or a table). Thecomputer system can wirelessly communicate to the interrogator, forexample through a network connection, a radiofrequency (RF) connection,or Bluetooth. The computer system may, for example, turn on or off theinterrogator or analyze information encoded in ultrasonic waves receivedby the interrogator.

Communication Between an Implantable Device and an Interrogator

The implantable device and the interrogator wirelessly communicate witheach other using ultrasonic waves. The implantable device receivesultrasonic waves from the interrogator through one or more ultrasonictransducers on the implantable device, and the ultrasonic waves canencode instructions for operating the implantable device. Vibrations ofthe ultrasonic transducer(s) on the implantable device generate avoltage across the electric terminals of the transducer, and currentflows through the device, including the integrated circuit. The currentcan be used to charge an energy storage circuit, which can store energyto be used to emit an electrical pulse, for example after receiving atrigger signal. The trigger signal can be transmitted from theinterrogator to the implantable device, signaling that an electricalpulse should be emitted. In some embodiments, the trigger signalincludes information regarding the electrical pulse to be emitted, suchas frequency, amplitude, pulse length, or pulse shape (e.g., alternatingcurrent, direct current, or pulse pattern). A digital circuit candecipher the trigger signal and operate the electrodes and electricalstorage circuit to emit the pulse.

In some embodiments, ultrasonic backscatter is emitted from theimplantable device, which can encode information relating to theimplantable device, the electrical pulse emitted by the implantabledevice, an electrophysiological pulse detected by the implantabledevice, or a detected physiological condition. For example, theultrasonic backscatter can encode a verification signal, which verifiesthat electrical pulse was emitted. In some embodiments, an implantabledevice is configured to detect an electrophysiological signal, andinformation regarding the detected electrophysiological signal can betransmitted to the interrogator by the ultrasonic backscatter. To encodesignals in the ultrasonic backscatter, current flowing through theultrasonic transducer(s) of the implantable device is modulated as afunction of the encoded information, such as a detectedelectrophysiological signal or measured physiological condition. In someembodiments, modulation of the current can be an analog signal, whichmay be, for example, directly modulated by the detectedelectrophysiological signal. In some embodiments, modulation of thecurrent encodes a digitized signal, which may be controlled by a digitalcircuit in the integrated circuit. The backscatter is received by anexternal ultrasonic transceiver (which may be the same or different fromthe external ultrasonic transceiver that transmitted the initialultrasonic waves). The information from the electrophysiological signalcan thus be encoded by changes in amplitude, frequency, or phase of thebackscattered ultrasound waves.

FIG. 11 shows an interrogator in communication with an implantabledevice. The external ultrasonic transceiver emits ultrasonic waves(“carrier waves”), which can pass through tissue. The carrier wavescause mechanical vibrations on the ultrasonic transducer (e.g., a bulkpiezoelectric transducer, a PUMT, or a CMUT). A voltage across theultrasonic transducer is generated, which imparts a current flowingthrough an integrated circuit on the implantable device. The currentflowing through to the ultrasonic transducer causes the transducer onthe implantable device to emit backscatter ultrasonic waves. In someembodiments, the integrated circuit modulates the current flowingthrough the ultrasonic transducer to encode information, and theresulting ultrasonic backscatter waves encode the information. Thebackscatter waves can be detected by the interrogator, and can beanalyzed to interpret information encoded in the ultrasonic backscatter.

Communication between the interrogator and the implantable device canuse a pulse-echo method of transmitting and receiving ultrasonic waves.In the pulse-echo method, the interrogator transmits a series ofinterrogation pulses at a predetermined frequency, and then receivesbackscatter echoes from the implanted device. In some embodiments, thepulses are square, rectangular, triangular, sawtooth, or sinusoidal. Insome embodiments, the pulses output can be two-level (GND and POS),three-level (GND, NEG, POS), 5-level, or any other multiple-level (forexample, if using 24-bit DAC). In some embodiments, the pulses arecontinuously transmitted by the interrogator during operation. In someembodiments, when the pulses are continuously transmitted by theinterrogator a portion of the transducers on the interrogator areconfigured to receive ultrasonic waves and a portion of the transducerson the interrogator are configured to transmit ultrasonic waves.Transducers configured to receive ultrasonic waves and transducersconfigured to transmit ultrasonic waves can be on the same transducerarray or on different transducer arrays of the interrogator. In someembodiments, a transducer on the interrogator can be configured toalternatively transmit or receive the ultrasonic waves. For example, atransducer can cycle between transmitting one or more pulses and a pauseperiod. The transducer is configured to transmit the ultrasonic waveswhen transmitting the one or more pulses, and can then switch to areceiving mode during the pause period.

In some embodiments, the backscattered ultrasound is digitized by theimplantable device. For example, the implantable device can include anoscilloscope or analog-to-digital converter (ADC) and/or a memory, whichcan digitally encode information in current (or impedance) fluctuations.The digitized current fluctuations, which can encode information, arereceived by the ultrasonic transducer, which then transmits digitizedacoustic waves. The digitized data can compress the analog data, forexample by using singular value decomposition (SVD) and leastsquares-based compression. In some embodiments, the compression isperformed by a correlator or pattern detection algorithm. Thebackscatter signal may go through a series of non-linear transformation,such as 4^(th) order Butterworth bandpass filter rectificationintegration of backscatter regions to generate a reconstruction datapoint at a single time instance. Such transformations can be done eitherin hardware (i.e., hard-coded) or in software.

In some embodiments, the digitized data can include a unique identifier.The unique identifier can be useful, for example, in a system comprisinga plurality of implantable devices and/or an implantable devicecomprising a plurality of electrode pairs. For example, the uniqueidentifier can identify the implantable device of origin when from aplurality of implantable devices, for example when transmittinginformation from the implantable device (such as a verification signal).In some embodiments, an implantable device comprises a plurality ofelectrode pairs, which may simultaneously or alternatively emit anelectrical pulse by a single implantable device. Different pairs ofelectrodes, for example, can be configured to emit an electrical pulsein different tissues (e.g., different nerves or different muscles) or indifferent regions of the same tissue. The digitized circuit can encode aunique identifier to identify and/or verify which electrode pairsemitted the electrical pulse.

In some embodiments, the digitized signal compresses the size of theanalog signal. The decreased size of the digitized signal can allow formore efficient reporting of information encoded in the ultrasonicbackscatter. By compressing the size of the transmitted informationthrough digitization, potentially overlapping signals can be accuratelytransmitted.

In some embodiments, an interrogator communicates with a plurality ofimplantable devices. This can be performed, for example, usingmultiple-input, multiple output (MIMO) system theory. For example,communication between the interrogator and the plurality of implantabledevices using time division multiplexing, spatial multiplexing, orfrequency multiplexing. The interrogator can receive a combinedbackscatter from the plurality of the implantable devices, which can bedeconvoluted, thereby extracting information from each implantabledevice. In some embodiments, interrogator focuses the ultrasonic wavestransmitted from a transducer array to a particular implantable devicethrough beam steering. The interrogator focuses the transmittedultrasonic waves to a first implantable device, receives backscatterfrom the first implantable device, focuses transmitted ultrasonic wavesto a second implantable device, and receives backscatter from the secondimplantable device. In some embodiments, the interrogator transmitsultrasonic waves to a plurality of implantable devices, and thenreceives ultrasonic waves from the plurality of implantable devices.

Methods of Implanting the Implantable Device

The implantable device having a body and a clip attached to the body canbe implanted in a subject to maneuver the legs of the clip to at leastpartially surround a nerve and/or filamentous tissue attached to thenerve, such as a blood vessel or tendon. The body includes one or moreultrasonic transducers configured to receive ultrasonic waves andconvert energy from the ultrasonic waves into an electrical energy thatpowers the device. The device further includes one or more electrodes inelectrical communication with the ultrasonic transducer, for examplethrough an integrated circuit as described herein. The electrodes may bepositioned on the legs of the implantable device, or on the body (suchas underneath the body) of the implantable device. In some embodiments,the device is laparoscopically implanted.

In one example, implanting the device in a subject can include outwardlyflexing one or more of the legs of the clip, and positioning theelectrodes to be in electrical communication with the nerve. In someembodiments, the electrodes are positioned to directly contact thenerve. In some embodiments, the two or more electrodes are positionedwithin about 2 mm (within about 1.8 mm, within about 1.6 mm, withinabout 1.4 mm, within about 1.2 mm, within about 1.0 mm, within about 0.8mm, within about 0.6 mm, within about 0.4 mm, or within about 0.2 mm ofthe nerve. The one or more flexed legs are released to allow the legs ofthe clam to at least partially surround the nerve and/or filamentoustissue attached to the nerve. With the legs partially surrounding thenerve, the electrodes are maintained in electrical communication withthe nerve once the legs are released.

The implantable device may include one or more hooks or loops configuredto maneuver one or more legs of the clip. For example, as shown in FIG.9B, hook 918 can be pushed downward to force leg 916 to flex outwardly.With leg 916 flexed outwardly, the implantable device can be positionedto put the electrodes (which may be on leg 916 or on body 914) inelectrical communication with the nerve. Hook 918 can be released, whichreleases leg 916 and allows leg 916 to close inwardly, thereby at leastpartially surrounding the nerve. The hooks or loops may be pushedupwardly, pushed downwardly, pushed laterally, or pulled to maneuver thelegs of the clip.

The implantable device can be implanted so that the electrodes are incontact with, or the legs of the clip at least partially surround, anautonomic nerve. In some embodiments, the nerve is a sympathetic nerve.In some embodiments, the never is a vagus nerve, a mesenteric nerve, asplenic nerve, a sciatic nerve, a tibial nerve, a pudendal nerve, aceliac ganglion, a sacral nerve, or any branch thereof.

Methods of Using the Implantable Device

The implantable device is operated using an interrogator, which cantransmit ultrasonic waves that power and operate the implantable device.The implantable device can be used in at least one of three basic modesof operation. First, the implantable device can be operated to emit anelectrical pulse to a tissue. The electrical pulse may be applied to anerve to stimulate neural activity or to block neural activity.Optionally, the electrically pulse may be emitted in response to theimplantable device receiving a trigger signal encoded in ultrasonicwaves transmitted by an interrogator. Further, the implantable deviceoptionally encodes information related to the emitted electrical pulse(such as an affirmation that the pulse was emitted, a voltage of thepulse, or a pulse frequency) in ultrasonic backscatter waves, which canbe received by an interrogator and analyzed to decode the information.Second, the implantable device can be operated to detect neural activityand transmit information related to the detected neural activity.Electrodes on the implantable device in electrical communication with anerve can detect an electrophysiological pulse from the nerve, andinformation related to the electrophysiological pulse (e.g., frequency,voltage, shape, etc.) is encoded in the ultrasonic backscatter wavesemitted by the one or more ultrasonic transducers on the implantabledevice. The ultrasonic backscatter waves encoding the information can bereceived by an interrogator and analyzed to decode the information.Third, the implantable device may include a sensor that can measure aphysiological condition (e.g., pH, temperature, strain, tissueimpedance, or concentration of an analyte, such as oxygen), andinformation related to the measured physiological condition may beencoded in ultrasonic backscatter waves emitted by the implantabledevice. The ultrasonic backscatter waves encoding information related tothe measured physiological condition can be received by an interrogatorand analyzed to decode the information related to the physiologicalcondition.

In some embodiments, the three modes of operation support each other inthe device to safely treat a medical condition. For example, theinterrogator may transmit a trigger signal in ultrasonic waves based oninformation received by the implantable device relating to a measuredphysiological condition or a detected electrophysiological pulse. Forexample, an irregular electrophysiological pulse or electrophysiologicalpulse pattern may be treated by emitting one or more electrical pulsesfrom the implantable device. The implantable device may detect one ormore electrophysiological pulses from a nerve, and emit an ultrasonicbackscatter encoding information related to the electrophysiologicalpulse. The ultrasonic backscatter can be received by an interrogator,which decodes the information and recognizes the electrophysiologicalpulse or electrophysiological pulse pattern as indicative of the needfor an electrical pulse to be applied to the nerve. The interrogator canthen transmit a trigger signal encoded in ultrasonic waves to theimplantable device, thereby operating the implantable device to emit anelectrical pulse. The measured physiological condition may also impactthe decision of whether to operate the implantable device to emit anelectrical pulse. For example, an elevated temperature measured by theimplantable device may indicate that the electrical pulse should not beemitted. The interrogator may therefore transmit the trigger signalbased on the detected electrophysiological pulse or electrophysiologicalpulse pattern, and/or the measured physiological condition.

The trigger signal transmitted by the interrogator can includeinstructions for emitting the electrical pulse, and may includeinstructions for the type of pulse (e.g., direct current pulse oralternating current pulse), a number pulses, a dwell time betweenpulses, a pulse frequency, a pulse amplitude, a pulse shape, or a pulsevoltage. As discussed above, transmission of the trigger signal may bebased on information related to a detected electrophysiological pulse,detected electrophysiological pulse pattern, or a measured physiologicalcondition.

In some embodiments, the electrical pulse emitted by the implantabledevice is a direct current pulse or an alternating current pulse. Insome embodiments, the electrical pulse comprises a plurality of pulses,which may be separated by a dwell time. In some embodiments, theelectrical pulse is about 1 microsecond (μs) or longer (such as about 5μs or longer, about 10 μs or longer, about 20 μs or longer, about 50 μsor longer, about 100 μs or longer, about 250 μs or longer, about 500 μsor longer, about 1 millisecond (ms) or longer, about 5 ms or longer,about 10 ms or longer, about 25 ms or longer, about 50 ms or longer,about 100 ms or longer, about 200 ms or longer, or about 500 ms orlonger). In some embodiments, the electrical pulse is about 1000 ms orshorter (such as about 500 ms or shorter, about 200 ms or shorter, about100 ms or shorter, or about 50 ms or shorter, about 25 ms or shorter,about 10 ms or shorter, about 5 ms or shorter, about 1 ms or shorter,about 500 μs or shorter, about 250 μs or shorter, about 100 μs orshorter, about 50 μs or shorter, about 20 μs or shorter, about 10 μs orshorter, or about 5 μs or shorter). In some embodiments, the dwell timeis about 1 microsecond (μs) or longer (such as about 5 μs or longer,about 10 μs or longer, about 20 μs or longer, about 50 μs or longer,about 100 μs or longer, about 250 μs or longer, about 500 μs or longer,about 1 millisecond (ms) or longer, about 5 ms or longer, about 10 ms orlonger, about 25 ms or longer, or about 50 ms or longer). In someembodiments, the dwell time is about 100 ms or shorter (such as about 50ms or shorter, about 25 ms or shorter, about 10 ms or shorter, about 5ms or shorter, about 1 ms or shorter, about 500 μs or shorter, about 250μs or shorter, about 100 μs or shorter, about 50 μs or shorter, about 20μs or shorter, about 10 μs or shorter, or about 5 μs or shorter).

In some embodiments, the electrical pulse is about 1 microamp (μA) ormore (such as about 5 μA or more, about 10 μA or more, about 25 μA ormore, about 50 μA or more, about 100 μA or more, about 250 μA or more,about 500 μA or more, about 1 milliamp (mA) or more, about 5 mA or more,about 10 mA or more, or about 25 mA or more). In some embodiments, theelectrical pulse is about 50 mA or less (such as about 25 mA or less,about 10 mA or less, about 5 mA or less, about 1 mA or less, about 500μA or less, about 250 μA or less, about 100 μA or less, about 50 μA orless, about 25 μA or less, about 10 μA or less, about 5 μA or less, orabout 1 μA or less.

In some embodiments, the electrical pulse has a current frequency ofabout 0.1 Hz or more (such as about 0.5 Hz or more, about 1 Hz or more,about 5 Hz or more, about 10 Hz or more, about 25 Hz or more, about 50Hz or more, about 100 Hz or more, about 200 Hz or more, about 300 Hz ormore, about 400 Hz or more, about 500 Hz or more about 600 Hz or more,about 700 Hz or more, about 800 Hz or more, about 1 kHz or more, about 2kHz or more, or about 5 kHz or more). In some embodiments, theelectrical pulse has a current frequency of about 10 kHz or less (suchas about 5 kHz or less, about 2 kHz or less, about 1 kHz or less, about800 Hz or less, about 700 Hz or less, about 600 Hz or less, about 500 Hzor less, about 400 Hz or less, about 300 Hz or less, about 200 Hz orless, about 100 Hz or less, about 50 Hz or less, about 25 Hz or less,about 10 Hz or less, about 5 Hz or less, about 1 Hz or less, or about0.5 Hz or less).

In some embodiments, the implantable device generates a voltage pulse inthe tissue. In some embodiments, the voltage is about 50 mV or more(such as about 100 mV or more, about 250 mV or more, about 500 mV ormore about 1 V or more, about 2.5 V or more, about 5 V or more, or about10 V or more). In some embodiments, the voltage is about 20 V or less(such as about 15 V or less, about 10 V or less, about 5 V or less,about 2.5 V or less, about 1 V or less, about 500 mV or less, about 250mV or less, or about 100 mV or less).

Features of the electrical pulse, such as frequency, amplitude, andlength, can affect the impact of the electrical pulse on the neuraltissue. For example, lower frequency pulses (such as those less thanabout 1 kHz) can stimulate neural activity, whereas higher frequencypulses (such as those greater than about 1 kHz) can block neuralactivity.

Methods of Treating Incontinence

In some embodiments, the implantable device described herein is used totreat incontinence in a patient, such as an overactive bladder, anunderactive bladder, urinary incontinence, or fecal incontinence. Theimplantable device can be fully implanted in the subject such that theelectrodes are in electrical communication with a tibial nerve or abranch thereof, a pudendal nerve or branch thereof, or a sacral nerve ora branch thereof, and the nerve can be electrically stimulated using thefully implanted medical device. In some embodiments, the implantabledevice electrically stimulates the nerve by emitting one or moreelectrical pulses that block neurological activity of the nerve. In someembodiments, the implantable device electrically stimulates the nerve byemitting one or more electrical pulses that activates neurologicalactivity of the nerve. Electrical stimulation by emitting one or moreelectrical pulses (e.g., current pulses or voltage pulses) may be inresponse to a trigger signal encoded in ultrasonic waves received by theimplantable device. As discussed above, transmission of the triggersignal may be based on a detected electrophysiological pulse or pulsepattern, or a measured physiological condition, which may be transmittedfrom the implantable device using ultrasonic backscatter.

The electrical pulses may be emitted by the implantable device at aconstant frequency. The length of time that the electrical pulses areemitted may be predetermined, or may be based on a detectedelectrophysiological pulse or pulse pattern, or by a measuredphysiological condition, as described herein. In some embodiments, thefrequency of the electrical pulses is between about 0.1 Hz and about 500Hz, such as between about 0.2 Hz and about 250 Hz, between about 0.5 Hzand about 100 Hz, between about 1 Hz and about 50 Hz, or between about 5Hz and about 30 Hz.

The interrogator can be externally worn by the subject, and can operateand power the implantable device, and the ultrasonic transducers on theinterrogator preferably contact the skin of the subject. In someembodiments, the ultrasonic transducers of the interrogator are about 10cm or less, about 5 cm or less, about 4 cm or less, about 3 cm or less,about 2 cm or less, or about 1 cm or less from the implantable device.Positioning of the interrogator depends on the positioning of theimplantable device and which nerve is in electrical communication withthe electrodes of the implantable device. For example, if theimplantable device includes electrodes that are in electricalcommunication with a sacral nerve, the interrogator can be positioned onthe hip, abdomen, lower back, buttocks, or upper leg of the patient. Ifthe implantable device includes electrodes that are in electricalcommunication with a tibial nerve, the interrogator can be positioned onthe lower leg (e.g., calf) or ankle of the subject. The interrogator canbe positioned using an adhesive that fixes to the skin of the subject, aband, or can be a hand-held device positioned in the desired location.

By way of example, percutaneous tibial nerve stimulation (PTNS) is aknown treatment for incontinence and related disorders, such asoveractive bladder, urinary incontinence, and fecal incontinence. Knowndevices stimulate the tibial nerve by placing a needle electrode nearthe tibial nerve in the ankle by passing it through the skin. One leadof the device is connected to the exposed end of the electrode and theother lead is connected to a return electrode, which may be a conductivepad placed on the skin of the patient (such as on the foot). Duringtreatment, current or voltage pulses are delivered at a constantfrequency (for example, between 5 Hz and 30 Hz), and stimulationintensity is increased until there is movement in the patient's toe.Treatment continues for approximately 30 minutes, and is generallyperformed in a doctor's office once per week for 12 weeks, followed bylonger interval maintenance treatments. Although this treatment isgenerally effective, there is substantial patient discomfort in regularneedle insertions, and the treatment is inconvenient in that it requiresfrequent doctor visits. The system described herein provides asignificantly more convenient treatment regimen, which can be performedin home and with increased frequency.

FIG. 13A shows an implantable device with a body and a clip fullyimplanted in a subject, wherein the clip attaches the implantable deviceto the tibial nerve. The body of the implantable device includeselectrodes in electrical communication with the tibial nerve, and anultrasonic transducer configured to receive ultrasonic waves that powerand operate the device. The clip includes legs that surround the tibialnerve, and retain the electrodes in electrical contact with the nerve.The tibial nerve can be stimulated by converting energy from ultrasonicwaves into an electrical energy to power the device, and electricallystimulating the tibial nerve in response to a trigger signal encoded inthe ultrasonic waves. The ultrasonic waves received by the device can betransmitted by an interrogator, as shown in FIG. 13B. The interrogatoris worn by the patient at the ankle. As illustrated in FIG. 13B, theultrasonic transducers of the interrogator are positioned against theskin. Optionally, the interrogator is controlled by a computer system,such as a mobile device.

Sacral nerve stimulation is another method known to be used to treatcertain urinary disorders such as an overactive bladder. Treatment caninclude continuous electrical stimulation of the sacral nerve toincrease a time interval between urinary voids and to reduce a feelingof urgency to void the bladder. Known devices for sacral nervestimulation generally include leads that are placed near the sacralnerve connected to an implanted pulse generator that contains a battery.The device can be surgically placed under the skin, usually in the lowerabdomen near the hip. However, because these devices require a battery,the battery can wear out, requiring surgery to replace the device.Further, the leads of the device can break, again requiring surgery toremove the broken lead and replace device. Further, the surgical pocketis relatively large, and is subject to infection. Because of theseconcerns, many patients elect not to undergo sacral nerve stimulationtreatment. However, the implantable device described herein is muchsmaller than known devices, thereby minimizing risk of infection.Additionally, the small size of the device described herein allows theimplantable device to be secured directly on the sacral nerve, therebyavoiding the need for electrical leads that are subject to breakage.Further, because the device is powered by ultrasonic waves, the deviceis batteryless and there is no need to remove the device due to afailing battery.

FIG. 14 shows the system being used for sacral nerve stimulation (SNS).The implantable device includes a body having an ultrasonic transducer,electrodes, and a clip. The clip surrounds the sacral nerve to positionthe electrode in electrical communication with the sacral nerve. Theultrasonic transducer on the implantable device is configured to receiveultrasonic waves that power and operate the device. For example, theultrasonic waves can optionally include a trigger signal that instructsthe device to stimulate the nerve. The implantable device may beconfigured to continuously stimulate the nerve, and the ultrasonic wavesmay instruct the implantable device to begin to stop continuousstimulation. The implantable device may also emit an ultrasonicbackscatter that encodes information related to the status of the deviceor about electrical pulses emitted by the device. An externalinterrogator can be worn by the subject, which can transmit theultrasonic waves to the implantable device. The interrogator may includea battery that can be replaced or recharged. Optionally, theinterrogator communicates with a computer system, such as a mobiledevice (e.g., a smartphone or tablet), which can turn on or off thesystem.

EXEMPLARY EMBODIMENTS Embodiment 1

An implantable medical device, comprising:

a body comprising an ultrasonic transducer configured to receiveultrasonic waves and convert energy from the ultrasonic waves into anelectrical energy that powers the device;

two or more electrodes in electrical communication with the ultrasonictransducer; and

a clip attached to the body that is configured to at least partiallysurround a nerve and position the two or more electrodes in electricalcommunication with the nerve.

Embodiment 2

The implantable medical device of embodiment 1, wherein the clip isconfigured to at least partially surround the nerve and a filamentoustissue attached to the nerve.

Embodiment 3

The implantable medical device of embodiment 2, wherein the filamentoustissue is a blood vessel.

Embodiment 4

The implantable medical device of any one of embodiments 1-3, whereinthe clip comprises a plurality of flexible legs that extend below thebody.

Embodiment 5

The implantable device of embodiment 4, wherein the implantable devicecomprises a hook or loop configured to maneuver at least one of theflexible legs in response to maneuvering the hook or loop.

Embodiment 6

The implantable device of embodiment 5, wherein the hook or loop ispositioned at a terminus of one of the flexible legs.

Embodiment 7

The implantable device of embodiment 5, wherein the hook or loop ispositioned proximal to the body.

Embodiment 8

The implantable medical device of any one of embodiments 4-7, whereinthe flexible legs are curved.

Embodiment 9

The implantable medical device of embodiment 8, wherein the legs extendaway from the body before curving toward the body as the legs extendbelow the body.

Embodiment 10

The implantable medical device of embodiment 9, wherein the plurality offlexible legs comprises at least one pair of legs, wherein the pair oflegs comprises a first leg and a second leg that extend away from andbelow the body in opposite directions.

Embodiment 11

The implantable medical device of embodiment 10, wherein the first legand the second leg are connected by a crossbar connected to the body.

Embodiment 12

The implantable medical device of embodiment 11, wherein the crossbar isconnected to the body of the device through a flexible member.

Embodiment 13

The implantable medical device of embodiment 12, wherein the flexiblemember is a hinge.

Embodiment 14

The implantable medical device of any one of embodiments 10-13, whereinthe device comprises two pairs of legs, wherein each pair of leg ispositioned on opposite sides of the body.

Embodiment 15

The implantable medical device of any one of embodiments 4-14, whereinthe legs are attached to the body through a bottom surface of the body.

Embodiment 16

The implantable medical device of any one of embodiments 4-14, whereinthe legs are attached to the body through a sidewall of the body.

Embodiment 17

The implantable medical device of any one of embodiments 4-16, whereinthe legs comprise a metal, metal alloy, ceramic, silicon, or anon-polymeric material.

Embodiment 18

The implantable medical device of any one of embodiments 4-17, whereinthe legs comprise an elastomeric coating or a non-elastomeric polymercoating.

Embodiment 19

The implantable medical device of embodiment 18, wherein the coating isbioinert.

Embodiment 20

The implantable medical device of embodiment 18 or 19, wherein thecoating is a silicone, a poly(p-xylylene) polymer, or a polyimide.

Embodiment 21

The implantable medical device of any one of embodiments 18-20, whereinat least one of the legs comprises an outer surface coated with theelastomeric coating or the non-elastomeric polymer coating and an innersurface comprising at least one electrode that is not coated with theelastomeric coating or the non-elastomeric polymer coating.

Embodiment 22

The implantable medical device of any one of embodiments 1-21, whereinthe body comprises a bottom surface, and the two or more electrodes areterminate on the bottom of the body.

Embodiment 23

The implantable medical device of any one of embodiments 1-21, whereinthe two or more electrodes are positioned on the clip.

Embodiment 24

The implantable medical device of embodiment 23, wherein the clipcomprises a plurality of flexible legs that extend below the body, andthe two or more electrodes are positioned on the flexible legs.

Embodiment 25

The implantable medical device of any one of embodiments 1-24, whereinthe body comprises a housing.

Embodiment 26

The implantable medical device of embodiment 17, wherein the housingcomprises or is coated with a bioinert material.

Embodiment 27

The implantable medical device of embodiment 26, wherein the housingcomprises the bioinert material, and wherein the bioinert material ofthe housing comprises titanium or a ceramic.

Embodiment 28

The implantable medical device of any one of embodiments 1-27, whereinthe body comprises an integrated circuit electrically connected to theultrasonic transducer and the two or more electrodes.

Embodiment 29

The implantable medical device of embodiment 28, wherein the integratedcircuit comprises an energy storage circuit comprising a capacitor.

Embodiment 30

The implantable medical device of any one of embodiments 1-29, whereinthe body is about 5 mm or less in length in the longest dimension.

Embodiment 31

The implantable medical device of any one of embodiments 1-30, whereinthe ultrasonic transducer is configured to emit an ultrasonicbackscatter that encodes data.

Embodiment 32

The implantable medical device of embodiment 31, wherein the datacomprises information related to a detected neural activity, a measuredphysiological condition, a device status, or an emitted electricalpulse.

Embodiment 33

The implantable medical device of any one of embodiments 1-32, whereinthe implantable medical device is configured to emit an electrical pulseto the nerve.

Embodiment 34

The implantable medical device of any one of embodiments 1-33, whereinthe ultrasonic transducer is configured to receive ultrasonic waves thatencode instructions for operating the implantable device.

Embodiment 35

The implantable medical device of embodiment 34, wherein theinstructions comprise a trigger signal that operates the implantabledevice to emit an electrical pulse to the nerve.

Embodiment 36

A method of implanting a medical device in a subject, the devicecomprising a body comprising an ultrasonic transducer configured toreceive ultrasonic waves and convert energy from the ultrasonic wavesinto an electrical energy that powers the device, electrodes inelectrical communication with the ultrasonic transducer, and a clipattached to the body, wherein the clip comprises a plurality of flexiblelegs, the method comprising:

outwardly flexing one or more legs of the clip;

positioning the electrodes to be in electrical communication with anerve; and

releasing the one or more legs of the clip, where the one or more legsat least partially surrounds the nerve and maintains the electrodes inelectrical communication with the nerve upon release.

Embodiment 37

The method of embodiment 36, wherein the plurality of legs at leastpartially surrounds the nerve and a filamentous tissue attached to thenerve.

Embodiment 38

The method of embodiment 37, wherein the filamentous tissue is a bloodvessel.

Embodiment 39

The method of any one of embodiments 36-38, wherein the device islaparoscopically implanted in the subject.

Embodiment 40

The method of any one of embodiments 36-39, wherein the clip exerts aninward pressure on the nerve.

Embodiment 41

The method of any one of embodiments 36-40, wherein the clip allows forrotational movement around the nerve.

Embodiment 42

The method of any one of embodiments 36-41, wherein the nerve is anautonomic nerve.

Embodiment 43

The method of anyone of embodiments 36-42, wherein the nerve is asympathetic nerve.

Embodiment 44

The method of any one of embodiments 36-43, wherein the nerve is amesenteric nerve, a splenic nerve, a sciatic nerve, a tibial nerve, aceliac ganglion, or a sacral nerve.

Embodiment 45

The method of any one of embodiments 36-44, wherein the legs exert apressure on the nerve or the filamentous tissue of about 1 MPa or less.

Embodiment 46

The method of any one of embodiments 36-45, wherein the plurality oflegs extend below the body.

Embodiment 47

The method of any one of embodiments 36-46, wherein outwardly flexingone or more legs of the clip comprises maneuvering one or more hooks orloops connected to the one or more legs.

Embodiment 48

The method of any one of embodiments 36-47, wherein the legs are curved.

Embodiment 49

The method of any one of embodiments 36-48, wherein the legs extend awayfrom the body before curving toward the body as the legs extend belowthe body.

Embodiment 50

The method of any one of embodiments 36-49, wherein the plurality offlexible legs comprises at least one pair of legs, wherein the pair oflegs comprises a first leg and a second leg that extend away from andbelow the body in opposite directions.

Embodiment 51

The method of embodiment 50, wherein the pair of legs are connected by acrossbar connected to the body.

Embodiment 52

The method of embodiment 51, wherein the crossbar is connected to thebody of the device through a flexible member.

Embodiment 53

The method of embodiment 52, wherein the flexible member is a hinge.

Embodiment 54

The method of any one of embodiments 36-53, wherein the device comprisestwo pairs of legs, wherein each pair of leg is positioned to oppositesides of the body.

Embodiment 55

The method of any one of embodiments 36-54, wherein the legs areattached to the body through a bottom surface of the body.

Embodiment 56

The method of any one of embodiments 36-54, wherein the legs areattached to the body through a sidewall of the body.

Embodiment 57

The method of any one of embodiments 36-56, wherein the legs comprise ametal, metal alloy, ceramic, silicon, or a non-polymeric material.

Embodiment 58

The method of any one of embodiments 36-57, wherein the legs comprise anelastomeric coating or a non-elastomeric polymer coating.

Embodiment 59

The method of embodiment 58, wherein the coating is bioinert.

Embodiment 60

The method of embodiment 58 or 59, wherein the coating is a silicone, aurethane polymer, a poly(p-xylylene) polymer, or a polyimide.

Embodiment 61

The method of any one of embodiments 58-60, wherein at least one of thelegs comprises an outer surface coated with the elastomeric coating orthe non-elastomeric polymer coating and an inner surface comprising atleast one electrode that is not coated with the elastomeric coating orthe non-elastomeric polymer coating.

Embodiment 62

The method of any one of embodiments 36-61, wherein the body comprises abottom surface, and the two or more electrodes are terminate on thebottom of the body.

Embodiment 63

The method of any one of embodiments 36-61, wherein the two or moreelectrodes are positioned on the clip.

Embodiment 64

The method of embodiment 63, wherein the clip comprises a plurality offlexible legs that extend below the body, and the two or more electrodesare positioned on the flexible legs.

Embodiment 65

The method of any one of embodiments 36-64, wherein the body comprises ahousing.

Embodiment 66

The method of embodiment 65, wherein the housing comprises a bioinertmaterial.

Embodiment 67

The method of embodiment 66, wherein the housing comprises the bioinertmaterial, and wherein the bioinert material of the housing comprisestitanium or a ceramic.

Embodiment 68

The method of any one of embodiments 36-67, wherein the body comprisesan integrated circuit electrically connected to the ultrasonictransducer and the two or more electrodes.

Embodiment 69

The method of embodiment 68, wherein the integrated circuit comprises anenergy storage circuit comprising a capacitor.

Embodiment 70

The method of any one of embodiments 36-69, wherein the body is about 5mm or less in length in the longest dimension.

Embodiment 71

An implantable medical device, comprising:

(a) two or more ultrasonic transducers configured to receive ultrasonicwaves that power the device and emit an ultrasonic backscatter;

(b) an integrated circuit comprising an energy storage circuitcomprising a capacitor, wherein the integrated circuit is electricallyconnected to the first ultrasonic transducer and the second ultrasonictransducer; and

(c) one or more of (i) a sensor configured to measure a physiologicalcondition, (ii) two or more electrodes configured to be in electricalcommunication with a tissue and emit an electrical pulse to the tissue,or (iii) two or more electrodes configured to be in electricalcommunication with a tissue and detect an electrophysiological signalfrom the tissue; wherein the sensor or the two or more electrodes areelectrically connected to the integrated circuit.

Embodiment 72

The implantable medical device of embodiment 71, wherein the two or moreultrasonic transducers comprise a first ultrasonic transducer comprisinga first polarization axis and a second ultrasonic transducer comprisinga second polarization axis, wherein the second ultrasonic transducer ispositioned so that the second polarization axis is orthogonal to thefirst polarization axis, and wherein the first ultrasonic transducer andthe second ultrasonic transducer are configured to receive theultrasonic waves that power the device and emit the ultrasonicbackscatter.

Embodiment 73

The implantable medical device of embodiment 71 and 72, wherein theimplantable device comprises the sensor configured to measure aphysiological condition.

Embodiment 74

The implantable medical device of embodiment 73, wherein the sensor is atemperature sensor, a pH sensor, a pressure sensor, a strain sensor, apulse sensor, a blood pressure sensor, an oxygen meter, a glucose meter,an impedance meter, or is configured to measure an analyteconcentration.

Embodiment 75

The implantable medical device of embodiment 71 or 72, wherein theimplantable device comprises the two or more electrodes configured to bein electrical communication with a tissue and emit an electrical pulseto the tissue.

Embodiment 76

The implantable medical device of embodiment 75, wherein the implantabledevice comprises the two or more electrodes configured to be inelectrical communication with a tissue and detect anelectrophysiological signal from the tissue.

Embodiment 77

The implantable medical device of embodiment 76, wherein theelectrophysiological signal is a neural signal.

Embodiment 78

The implantable medical device of any one of embodiments 71-77, whereinthe ultrasonic backscatter encodes information related to the measuredphysiological condition, the emitted electrical pulse, or the detectedelectrophysiological signal.

Embodiment 79

The implantable medical device of embodiment 78, wherein the two or moreultrasonic transducers are electrically connected to the integratedcircuit in parallel.

Embodiment 80

The implantable medical device of any one of embodiments 71-79, whereinthe two or more ultrasonic transducers and the integrated circuit arecontained within a body, the device further comprising a clip configuredto at least partially surround a filamentous tissue.

Embodiment 81

The implantable medical device of embodiment 80, wherein the filamentoustissue comprises a nerve.

Embodiment 82

The implantable medical device of embodiment 80, wherein the filamentoustissue comprises a nerve attached to a blood vessel.

Embodiment 83

The implantable medical device of embodiment 80, wherein the filamentoustissue comprises a nerve attached to a blood vessel.

Embodiment 84

The implantable medical device of embodiment any one of embodiments80-83, wherein the clip comprises a plurality of flexible legs thatextend below the body.

Embodiment 85

The implantable medical device of any one of embodiments 1-35 and 71-84,wherein the implantable medical device does not comprise a battery.

Embodiment 86

The implantable medical device of any one of embodiments 1-35 and 71-85,wherein the implantable medical device does not comprise aradiofrequency communication system.

Embodiment 87

The implantable medical device of any one of embodiments 1-35 and 71-86,wherein the implanted medical device does not comprise an electricallead that extends from the body of the device without terminating on aleg of a clip.

Embodiment 88

A system, comprising the implantable medical device of any one ofembodiments 1-35 and 71-87, and an interrogator comprising one or moreultrasonic transducers configured to transmit ultrasonic waves to theimplantable medical device, wherein the ultrasonic waves power theimplantable medical device.

Embodiment 89

The system of embodiment 88, wherein the interrogator is configured tobe worn externally.

Embodiment 90

The system of embodiment 88 or 89, wherein the interrogator isconfigured to receive ultrasonic backscatter emitted by the implantabledevice, wherein the ultrasonic backscatter encodes data.

Embodiment 91

The system of embodiment 90, wherein the interrogator is configured toanalyze the data or transmit the data to a computer system.

Embodiment 92

The system of any one of embodiments 88-91, wherein the ultrasonic wavestransmitted by the interrogator encode instructions for operating theimplantable device.

Embodiment 93

A method of treating incontinence in a subject, comprising:

converting energy from ultrasonic waves into electrical energy thatpowers a fully implanted medical device in the subject, the devicecomprising two or more electrodes in electrical communication with atibial nerve or a branch thereof, a pudendal nerve or a branch thereof,or a sacral nerve or a branch thereof of the subject; and

electrically stimulating the tibial nerve or the branch thereof, thepudendal nerve or the branch thereof, or the sacral nerve or the branchthereof, of the subject using the fully implanted medical device.

Embodiment 94

The method of embodiment 93, wherein the tibial nerve or the branchthereof, the pudendal nerve or the branch thereof, or the sacral nerveor the branch thereof is stimulated by the fully implanted medicaldevice in response to a trigger signal encoded in the ultrasonic waves.

Embodiment 95

The method of embodiment 93 or 94, wherein electrically stimulating thetibial nerve or the branch thereof, the pudendal nerve or the branchthereof, or the sacral nerve or the branch thereof comprises emitting aplurality of current pulses to the tibial nerve or the branch thereof,the pudendal nerve or the branch thereof, or the sacral nerve or thebranch thereof.

Embodiment 96

The method of embodiment 93 or 94, wherein electrically stimulating thetibial nerve or the branch thereof, the pudendal nerve or the branchthereof, or the sacral nerve or the branch thereof, comprises emitting aplurality of voltage pulses to the tibial nerve or the branch thereof,the pudendal nerve or the branch thereof, or the sacral nerve or thebranch thereof.

Embodiment 97

The method of embodiment 95 or 96, wherein the plurality or currentpulses or the plurality of voltage pulses are emitted at a constantfrequency.

Embodiment 98

The method of embodiment 97, wherein the frequency of the plurality ofcurrent pulses or the plurality of voltage pulses is between about 1 Hzand about 50 Hz.

Embodiment 99

The method of any one of embodiments 93-98, comprising transmitting theultrasonic waves to the implanted medical device using a interrogatorcomprising one or more ultrasonic transducers.

Embodiment 100

The method of embodiment 99, wherein the ultrasonic waves encodeinstructions for operating the implantable device.

Embodiment 101

The method of embodiment 99 or 100, comprising emitting an ultrasonicbackscatter that encodes data.

Embodiment 102

The method of embodiment 101, wherein the data comprises a stimulationstatus that indicates whether the implantable device emitted anelectrical pulse or what parameters were used to emit the electricalpulse.

Embodiment 103

The method of embodiment 101 or 102, comprising receiving the ultrasonicbackscatter.

Embodiment 104

The method of embodiment 103, comprising analyzing the data encoded bythe ultrasonic backscatter.

Embodiment 105

The method of any one of embodiments 93-104, wherein the interrogator isan externally worn device.

Embodiment 106

The method of any one of embodiments 93-105, wherein the interrogatorcontacts the skin of the subject.

Embodiment 107

The method of any one of embodiment 93-106, wherein the interrogator isoperated using a handheld device.

Embodiment 108

The method of embodiment 107, wherein the handheld device is wirelesslyconnected to the interrogator.

Embodiment 109

The method of any one of embodiments 93-108, comprising implanting themedical device in the subject to contact the two or more electrodes tothe tibial nerve or the branch thereof, the pudendal nerve or the branchthereof, or the sacral nerve or the branch thereof.

Embodiment 110

The method of any one of embodiments 93-109, wherein the two or moreelectrodes are in electrical communication with the tibial nerve or thebranch thereof.

Embodiment 111

The method of embodiment 110, wherein the interrogator is attached tothe ankle of the subject.

Embodiment 112

The method of any one of embodiments 93-109, wherein the two or moreelectrodes are in electrical communication with the sacral nerve or thebranch thereof.

Embodiment 113

The method of embodiment 112, wherein the interrogator is attached thehip, abdomen, lower back, buttocks, or upper leg of the patient.

Embodiment 114

The method of any one of embodiments 93-113, wherein the incontinence isan overactive bladder, an underactive bladder, urinary incontinence, orfecal incontinence.

Embodiment 115

The method of any one of embodiments 93-114, wherein the subject is ahuman.

Embodiment 116

The method of any one of embodiments 93-115, wherein the implantabledevice is the implantable medical device according to any one ofembodiments 1-35 and 71-87.

What is claimed is:
 1. An implantable medical device, comprising: a bodycomprising an ultrasonic transducer configured to receive ultrasonicwaves and convert energy from the ultrasonic waves into an electricalenergy that powers the device; two or more electrodes in electricalcommunication with the ultrasonic transducer; and a clip attached to thebody that is configured to at least partially surround a nerve andposition the two or more electrodes in electrical communication with thenerve, wherein the clip comprises one or more flexible legs and a hookor loop configured to maneuver the one or more flexible legs.
 2. Theimplantable medical device of claim 1, wherein the clip is configured toat least partially surround the nerve and a filamentous tissue attachedto the nerve.
 3. The implantable medical device of claim 2, wherein thefilamentous tissue is a blood vessel.
 4. The implantable medical deviceof claim 1, wherein the clip comprises a plurality of legs that extendbelow the body.
 5. The implantable medical device of claim 4, whereinthe legs are curved.
 6. The implantable medical device of claim 5,wherein the legs extend away from the body before curving toward thebody as the legs extend below the body.
 7. The implantable medicaldevice of claim 6, wherein the plurality of legs comprises at least onepair of legs, wherein the pair of legs comprises a first leg and asecond leg that extend away from and below the body in oppositedirections.
 8. The implantable medical device of claim 7, wherein thefirst leg and the second leg are connected by a crossbar connected tothe body.
 9. The implantable medical device of claim 8, wherein thecrossbar is connected to the body of the device through a flexiblemember.
 10. The implantable medical device of claim 4, wherein the legsare attached to the body through a bottom surface of the body.
 11. Theimplantable medical device of claim 4, wherein the legs comprise ametal, metal alloy, ceramic, silicon, or a non-polymeric material. 12.The implantable medical device of claim 11, wherein at least one of thelegs comprises an outer surface coated with the elastomeric coating orthe non-elastomeric polymer coating and an inner surface comprising atleast one electrode that is not coated with the elastomeric coating orthe non-elastomeric polymer coating.
 13. The implantable medical deviceof claim 4, wherein the legs comprise an elastomeric coating or anon-elastomeric polymer coating.
 14. The implantable medical device ofclaim 4, wherein the legs in the plurality of legs are flexible.
 15. Theimplantable medical device of claim 1, wherein the body comprises abottom surface, and the two or more electrodes terminate on the bottomof the body.
 16. The implantable medical device of claim 1, wherein thetwo or more electrodes are positioned on the clip.
 17. The implantablemedical device of claim 16, wherein the clip comprises a plurality oflegs that extend below the body, and the two or more electrodes arepositioned on the legs.
 18. The implantable medical device of claim 1,wherein the body comprises a housing.
 19. The implantable medical deviceof claim 1, wherein the body comprises an integrated circuitelectrically connected to the ultrasonic transducer and the two or moreelectrodes.
 20. The implantable medical device of claim 19, wherein theintegrated circuit comprises an energy storage circuit comprising acapacitor.
 21. The implantable medical device of claim 1, wherein thebody is 5 mm or less in length in the longest dimension.
 22. Theimplantable medical device of claim 1, wherein the ultrasonic transduceris configured to emit an ultrasonic backscatter that encodes data. 23.The implantable medical device of claim 22, wherein the data comprisesinformation related to a detected neural activity, a measuredphysiological condition, a device status, or an emitted electricalpulse.
 24. The implantable medical device of claim 1, wherein theimplantable medical device is configured to emit an electrical pulse tothe nerve.
 25. The implantable medical device of claim 1, wherein theultrasonic transducer is configured to receive ultrasonic waves thatencode instructions for operating the implantable device.
 26. Theimplantable medical device of claim 25, wherein the instructionscomprise a trigger signal that operates the implantable device to emitan electrical pulse to the nerve.
 27. The implantable medical device ofclaim 1, wherein the implantable medical device does not comprise abattery.
 28. The implantable medical device of claim 1, wherein theimplantable medical device does not comprise a radiofrequencycommunication system.
 29. The implantable medical device of claim 1,wherein the implanted medical device does not comprise an electricallead that extends from the body of the device without terminating on aleg of a clip.
 30. A system, comprising the implantable medical deviceof claim 1, and an interrogator comprising one or more ultrasonictransducers configured to transmit ultrasonic waves to the implantablemedical device, wherein the ultrasonic waves power the implantablemedical device.
 31. The system of claim 30, wherein the interrogator isconfigured to be worn externally.
 32. The system of claim 30, whereinthe interrogator is configured to receive ultrasonic backscatter emittedby the implantable device, wherein the ultrasonic backscatter encodesdata.
 33. The system of claim 32, wherein the interrogator is configuredto analyze the data or transmit the data to a computer system.
 34. Thesystem of claim 30, wherein the ultrasonic waves transmitted by theinterrogator encode instructions for operating the implantable device.35. A method of implanting a medical device in a subject, the devicecomprising a body comprising an ultrasonic transducer configured toreceive ultrasonic waves and convert energy from the ultrasonic wavesinto an electrical energy that powers the device, electrodes inelectrical communication with the ultrasonic transducer, and a clipattached to the body, wherein the clip comprises one or more flexiblelegs and a hook or loop configured to maneuver the one or more flexiblelegs, the method comprising: outwardly flexing the one or more flexiblelegs of the clip using the hook or loop; positioning the electrodes tobe in electrical communication with a nerve; and releasing the one ormore legs of the clip, where the one or more legs at least partiallysurrounds the nerve and maintains the electrodes in electricalcommunication with the nerve upon release.